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CYTOKINES & THEIR ROLE IN InFLAMMATION, PAIN & AGING
What are cytokines?
Cytokines are small secreted proteins released by cells that have a specific effect on the interactions and communications between cells. Cytokine is a general name; other names include lymphokine (cytokines made by lymphocytes), monokine (cytokines made by monocytes), chemokine (cytokines with chemotactic activities), and interleukin (cytokines made by one leukocyte and acting on other leukocytes). Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine action). There are both pro-inflammatory cytokines and anti-inflammatory cytokines. There is significant evidence showing that certain cytokines/chemokines are involved in not only the initiation but also the persistence of pathologic pain by directly activating nociceptive sensory neurons.
ANTI-INflammatory EFFECTS OF FLAVONOIDS & polyphenols
Inflammation plays a key role in diseases such as diabetes, asthma, cardiovascular diseases and cancer. Diet can influence different stages of inflammation and can have an important impact on several inflammatory diseases. Increasing scientific evidence has shown that polyphenolic compounds, such as flavonoids, which are found in fruits, vegetables, legumes, or cocoa, can have anti-inflammatory properties. Recent studies have demonstrated that flavonoids can inhibit regulatory enzymes or transcription factors important for controlling mediators involved in inflammation. Flavonoids are also known as potent antioxidants with the potential to attenuate tissue damage or fibrosis. Consequently, numerous studies in vitro and in animal models have found that flavonoids have the potential to inhibit the onset and development of inflammatory diseases.
Inflammaging refers to the chronic, low-grade inflammation that characterizes aging. Inflammaging is macrophage centered, involves several tissues and organs, including the gut microbiota, and is characterized by a complex balance between pro- and anti-inflammatory responses. Based on literature data, we argue that the major source of inflammatory stimuli is represented by endogenous/self, misplaced, or altered molecules resulting from damaged and/or dead cells and organelles (cell debris), recognized by receptors of the innate immune system. While their production is physiological and increases with age, their disposal by the proteasome via autophagy and/or mitophagy progressively declines. This ‘autoreactive/autoimmune’ process fuels the onset or progression of chronic diseases that can accelerate and propagate the aging process locally and systemically. Consequently, inflammaging can be considered a major target for antiaging strategies.
Non-opioid analgesics are commonly used to treat mild and moderate acute and chronic pain. Unlike opioids, long-term use of non-steroidal anti-inflammatory analgesics does not lead to physical dependence.
INGREDIENTS : Aconitum Carmichaelii Debx. Root •Aconitum Kusnezoffii Reichb. leaves •Acorus Calamus •Aloevera Barbedensis •Alpinia Officinarum Hance Root •Alternanthera Brasiliana Aerial parts •Anacardium Occidentalis Leaf •Andrographis Peniculata •Angelica Dahurica(Fisch.Ex Hoffm.)Benth. Ethook.F. Root •Angelica Pubescens Maxim.F.Biserrata Shan Et Yuan Root •Antrodia Camphorata •Aquilaria Sinensis(Lour.)Gilg •Ardisia Gigantifolia Stapf •Artemisia Absinthium •Artemisia Herba Alba •Asariradix Et Rhizoma •Asarum Sieboldii Miq. •Astragali Radix •Aucklandia Lappa Decne. Root •Averrhoa Carambola L. •Borassus Flabellifer L.(Arecaceae) Flowers •Boswellia Carterli Birdw •Boswellia Serrata Resin (Frankincense) •Caesalpinia Sappanl. •Callicarpa Formosana Rolfe •Campsis Grandiflora •Capsaicin •Cardiospermum Halicacabum L. •Carthamus Tinctorius L Flower •Chelidonium Majus •Cimifugin, From Root Of Saposhnikovia Divaricata •Cinnamomum Cassia Pres peel •Cinnamon Zeylanicum •Cissampelos Pareira •Cissus Quadrangularis •Clematis Chinensis Osbeck. •Collybolide, Collybia Maculata •Conolidine; An Indole Alkaloid Derived From Bark Of Tabernaemontana Divaricate •Conus Striatus venom •Corydalis Yanhusuo •Curcuma Alismatifolia •Curcuma Longal. Root •Curcumae Radix •Curcumin •Daemonorops Draco Bl. •Dalbergia Sissoo •Dalbergiae Odoriferae Lignum •Daphne Retusa •Desmodium Triflorum (Linn.) Dc. •Drymaria Cordata Willd •Elettaria Cardamonuum •Epibatidine •Erythrina Variegata Linn.peel •Eugenia Supra-Axillaris Spring. Ex Mart Leaf •Evodia Rutaecarpa (Juss.) Benth. Fruit •Ferula Assa-Foetida L. •Ficus Palmata L. Fruit •Flemingia Strobilifera •Fragaria Vesca •Fumaria Capreolata •Gentiana Kurroo Royle (Gentianaceae) Root •Harpagophytum •Holarrhena Antidysenterica leaves •Hydrocotyle Batrachium Hance •Hydrocotyle Umbellata L. (Acariçoba) Underground parts •Hyperforin And Hypericin •Illicium Verum Hook.F. Fruit •Impatiens Balsamina •Imperata Cylindrica Beauv. Var. Major (Nees)C.E.Hubb.Root •Jasminum Amplexicaule •Jdtic •Juglans Regia Leaf •Kadsura Interior A .C. Smith •Lactuca Scariola •Lamiophlomis Rotata (Benth)Kudo •Landolphia Owariensis •Lecaniodiscus Cupanioides Root •Leonurus Japonicus Sweet. •Ligularia Fischeri •Ligusticum Chuanxiong •Ligusticum Porteri •Litsea Monopetala (Lm) leaves s •Mallotus Repandus Stem •Mangiferin •Menispermum Dauricum Dc Root •Mentha Spicata •Mimosa Pudica •Mitragynine •Morinda Citrifolia •Moringa Oleifera Lam •Nardostachys Chinensis Batal.Root •Nigella Sativa Seeds •Nyctanthes Arbor-Tristis Linn. Stem Bark •Ocimum Basilicum L •Onosma Bracteatum •Opuntia Dillenii (Ker Gawl.) Haw. •Oroxylum Indicum (L.) Vent. Seed •Paederia Scandens (Lour.)Merr •Paeonia Lactiflora Pall. Root •Papaver Libanoticum •Paracetamol •Passion Fruit peel •Perilla Frutescens (L.) Britt. •Phoenix Sylvestris •Phyllanthus Amarus •Phyllanthus Corcovadensis •Phyllanthus Niruri •Phyllanthus Tenellus •Piper Betle L. leaves •Piper Longum L. •Pleurotus Eous Mushroom •Polygala Anatolica Boiss. Et Heldr •Polygala Japonica Houtt. •Polygonum Cuspidatum Sieb. Et Zucc Root •Polyphylla Paris Rhizome •Propolis •Psammosilene Tunicoides Root •Psychotria Sarmentosa Blume (Family: Rubiaceae) •Pterocephalus Hookeri •Punica Granatum (Flower) •Pycnogenol (Maritime Pine Bark) •Qianghuo Shengshi •Resveratrol •Ricinus Communis L. Seed •Rosa Damascena (Rosaceae) •Rosmarinic Acid •Rumex Crispus (Aerial) •Salvia Miltiorrhiza Bge.Root •Sargassum Ilicifolium Brown Seaweed •Solanum Torvum •Solanum Tuberosum L. peel •Spatholobus.Suberectus Dunn •Spilanthes Acmella Linn.Var.Oleracea Clarke •Stauntonia Chinensis Dc. •Stephania Japonica (Linn.) Leaf •Strychnos Nux-Vomica L. (Loganiaceae) •Termitomyces Albuminosus •Tetrahydropalmatine •Thuja Orientalis (More Pankh) •Typha Angustifolia Pollen •Uncaria Gambier(Hunter)Roxb. •Uncaria Tomentosa (Cat’s Claw) •Urtica Dioica (Aerial) •Vaccaria Segetalis (Neck.) Garcke Seed •Veronica Peregrina L •Vicoa Indica •Wilbrandia Ebracteata •Xanthium Sibiricum •Xanthium Strumarium L. •Zanthoxylum Nitidum (Roxb.) Dc. (Z. Nitidum) •Zingiber Officinale
SCIENCE:
Aconitum carmichaelii Debx. root extract
Background: Isotalatizidine is a representative C19-diterpenoid alkaloid extracted from the lateral roots of Aconitum carmichaelii, which has been widely used to treat various diseases on account of its analgesic, anti-inflammatory, anti-rheumatic, and immunosuppressive properties. The aim of this study was to evaluate the analgesic effect of isotalatizidine and its underlying mechanisms against neuropathic pain.
Methods: A chronic constrictive injury (CCI)-induced model of neuropathic pain was established in mice, and the limb withdrawal was evaluated by the Von Frey filament test following isotalatizidine or placebo administration. The signaling pathways in primary or immortalized microglia cells treated with isotalatizidine were analyzed by Western blotting and immunofluorescence.
Results: Intrathecal injection of isotalatizidine attenuated the CCI-induced mechanical allodynia in a dose-dependent manner. At the molecular level, isotalatizidine selectively increased the phosphorylation of p38 and ERK1/2, in addition to activating the transcription factor CREB and increasing dynorphin A production in cultured primary microglia. However, the downstream effects of isotalatizidine were abrogated by the selective ERK1/2 inhibitor U0126-EtOH or CREB inhibitor of KG-501, but not by the p38 inhibitor SB203580. The results also were confirmed in in vivo experiments.
Conclusion: Taken together, isotalatizidine specifically activates the ERK1/2 pathway and subsequently CREB, which triggers dynorphin A release in the microglia, eventually leading to its anti-nociceptive action.
Aconitum kusnezoffii Reichb. leaves extract
Diabetic peripheral neuropathy is a common chronic complication of diabetes. Routine clinical management uses analgesics to relieve pain in combination with drugs for nerve repair. The drugs are often not effective for the severe pain cases, and these western medications also have side effects. We report a more effective treatment of diabetic peripheral neuropathic pain using a high dose of a traditional Chinese medicine, aconitum (including both Radix aconite preparata and Radix aconite kusnezoffii), in combination with Huangqi Guizhi Wuwu Tang (i.e., astragalus, cassia twig, white peony root, and spatholobi). In order to achieve stronger analgesic effects, we increased the clinical dosage of aconitum from 15 to 120 g. The aconitum was boiled for 6–8 hours, and licorice was also used to reduce potential toxicities of aconitum. In the four reported cases, the patients’ neuropathic pain was remarkably reduced and the EMG profile was also improved with this treatment regimen. Adverse reactions were not observed during the therapy.
Thus, aconitum represents a promising and safe treatment for the well-being of patients and their diabetic peripheral neuropathic pain. Future controlled clinical trials using traditional Chinese medicines containing aconitum in treating the neuropathic pain are warranted.
Acorus calamus extract
Background: Acorus calamus (family: Araceae), is an indigenous plant, traditionally it is used as an ingredient of various cocktail preparations and for the management of severe inflammatory disorders in Indian system of medicine. Present study investigated the attenuating role of Acorus calamus plant extract in chronic constriction injury (CCI) of sciatic nerve induced peripheral neuropathy in rats.
Methods: Hot plate, plantar, Randall Selitto, Von Frey Hair, pin prick, acetone drop, photoactometer and rota-rod tests were performed to assess degree of thermal, radiant, mechanical, chemical sensation, spontaneous motor activity and motor co-ordination changes respectively, at different time intervals i.e., day 0, 1, 3, 6, 9, 12, 15, 18 and 21. Tissue myeloperoxidase, superoxide anion and total calcium levels were determined after 21st day to assess biochemical alterations. Histopathological evaluations were also performed. Hydroalcoholic extract of Acorus calamus (HAE-AC, 100 and 200 mg/kg, p.o.) and pregabalin (10 mg/kg, p.o.) were administered from the day of surgery for 14 days.
Results: CCI of sciatic nerve significantly induced thermal, radiant, mechanical hyperalgesia and thermal, chemical, tactile allodynia, along with increase in the levels of superoxide anion, total calcium and myeloperoxidase activity. Moreover significant histological changes were also observed. HAE-AC attenuated CCI induced development of painful behavioural, biochemical and histological changes in a dose dependent manner similar to that of pregabalin serving as positive control.
Conclusion: Acorus calamus prevented CCI induced neuropathy which may be attributed to its multiple actions including anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory actions.
Aloevera Barbedensis
Evaluation of anti-inflammatory activity and analgesic effect of Aloe vera leaf extract in rats
Clinical evaluation of analgesic and anti-inflammatory drugs envisages the development of side effects that makes efficacy of a drug arguable. Alternatively, indigenous drug with fewer side effects is the major thrust area of research in the management of pain and inflammation. In the present study aqueous extract of whole leaf of Aloe vera at various concentrations was investigated for its anti-inflammatory and analgesic activities in albino wistar rats. Carrageenan and formaldehyde-induced rat paw oedema was used to evaluate the anti-inflammatory activity and tail flick, hot plate and acetic acid tests were used to assess the analgesic activity of A. vera leaf aqueous extracts.
Whole leaf aqueous extracts at various concentrations (100, 200, 400, and 600 mg/kg of bw) significantly reduced formation of oedema induced by carrageenan and formaldehyde and granuloma formation in a dose dependent manner. Further, acetic acid-induced writhing model exhibited significant analgesic effect characterized by reduction in writhes. Whole leaf aqueous extract showed dose-dependent increase in tolerance to thermal stimulus comparable to indomethacin. No mortality was observed during the acute toxicity test at a dosage of 600mg/kg. Thus whole leaf aqueous extract of Aloe vera can be exploited as non toxic drug for the treatment and clinical management of inflammation and pain.
Alpinia officinarum Hance root extract
effect of Alpinia officinarum Hance alcohol extracts on primary dysmenorrheal
Objective: To study the effect of Alpinia officinarum Hance (A. officinarum) 80% alcohol extract on the primary dysmenorrhea.
Methods: A. officinarum 80% alcohol extract were enriched by macroporous adsorption resins. Female mice of primary dysmenorrhea model were established by oxytocin induction; the effects of A. officinarum 80% alcohol extract on primary dysmenorrhea were observed by body twist method; and the homogenate level of prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2) and Ca2+ in the uterus were observed in oxytocin-induced female mice.
Results: The writhing frequency of primary dysmenorrhea mice was significantly decreased after treatment of A. officinarum 80% alcohol extract and the level of PGF2α, PGE2 and Ca2+ in mice uterus was significantly decreased (P < 0.05, P < 0.01) in groups of mice treated with middle and high dosage of A. officinarum 80% alcohol extract compared with that of model group.
Conclusion: These findings suggest that A. Officinarum 80% alcohol extract can significantly relieve primary dysmenorrhea.
Alternanthera brasiliana aerial parts
analgesic properties of a hydroalcoholic extract obtained from Alternanthera brasiliana
The present study describes the analgesic effects of the hydroalcoholic extract (HE) obtained from the aerial parts of Alternanthera brasiliana in two models of pain in mice. Such an extract, given intraperitoneally or orally produced significant and long-lasting (0.5–4 h) antinociception when evaluated against acetic acid-induced abdominal constrictions. In the formalin test, the HE inhibited both the first and second phases of formalin-induced pain.
Furthermore, the HE was more potent than some standard drugs, such as aspirin, indomethacin and dipyrone, when evaluated against acetic acid-induced abdominal constrictions. These results suggest a strong analgesic effect for HE, possibly related to the presence of sterols, terpenes and phenolic compounds, confirming the popular use of A. brasiliana against dolorous processes.
Anacardium occidentalis leaf extract
Anacardium occidentalis (family: Anacardiaceae) is a plant of the tropical climate widely used by folklore to treat pain and inflammation. This study was conducted to evaluate the analgesic and anti-inflammatory effects of the leaf extracts in rat and mice using different models in other to confirm folkloric claims. The aqueous, hexane, dichloromethane and methanol extracts (AEAO, HEAO, DEAO and MEAO respectively) were investigated for analgesic effects in acetic acid induced pain in mice. They significantly reduced the number of writhing (p<0.001) and the highest analgesic effect was seen in DEAO extract. DEAO was further studied on various analgesic and anti-inflammatory models in graded doses. The extract significantly reduced writhing induced by acetic acid and the number and time of paw licking induced by formalin in a dose related manner. It inhibited the neurogenic and inflammatory phases of formalin. analgesia was shown in the inhibition of nociception induced by tail immersion in 55oC hot water. The extract prolonged the latencies of tail withdrawal to a similar degree as pentazocine.
The extract caused significant inhibition of carrageenan induced paw oedema in rats in a dose dependent manner. These findings suggest that the leaf extracts of Anacardium occidentalis are highly potent analgesic and anti-inflammatory agents. phytochemical analysis showed that the leaf extracts contain alkaloids, tannins, saponins and cardenolides.
Andrographis Peniculata
Andrographis paniculata (AP), a popular ingredient of Oriental folk medicine, is commonly used for treating infection, inflammation, fever and diarrhoea. In this study, extracts prepared from cultivated AP and their active constituent andrographolide were evaluated for antioxidant, antioedema and analgesic activities. The results showed that the aqueous AP extract (AP-H2O) exhibited a greater antioxidant activity than the ethanol AP extract (AP-EtOH) in all model systems tested. At a concentration of 50 µg/mL, the free radical scavenging, xanthine oxidase inhibition and antilipid peroxidation activities for AP-H2O were 66.8%, 57.3% and 65.3%, respectively, and for AP-EtOH were 57.8%, 52.6% and 34.2%, respectively. At a dosage of 100 mg/kg, AP-H2O and andrographolide, but not AP-EtOH, showed antioedema and analgesic activities.
In phytochemical analysis, AP-H2O showed a higher concentration of total flavanoid but a lower phenol content than AP-EtOH. In conclusion, AP-H2O was more potent than AP-EtOH in antioxidant activities. Furthermore, compared with andrographolide, AP-H2O as an extract also appears to possess potent antioedema and analgesic activities.
An analytically characterized extract of Andrographis paniculata leaves (AP) and isolated pure andrographolide were evaluated for their analgesic and anti-inflammatory activity in diabetic rodents. AP (100, 200 and 400 mg/kg/day, p.o.), or andrographolide (30, 60 and 120 mg/kg/day, p.o.) was administered for ten consecutive days. Pentazocine and indomethacin were used as standard analgesic and anti-inflammatory drugs, respectively. Diabetic control animals were demonstrated significant abnormal pain-associated behav- iours, measured as hyperalgesia to painful stimuli in tail flick test, hot plate test and formalin-evoked pain test, and exaggerated in- flammatory responses in carragennan-induced paw oedema and cotton pellet induced granuloma tests in comparison to nondiabetic control animals. AP and andrographolide treatments in diabetic animals demonstrated significant analgesic and anti-inflammatory activity in all these tests, and their maximal efficacies were always comparable to the standard drugs used.
Taken together, these observations confirm that andrographolide is the major active constituent of Andrographis paniculata, and strongly suggest that anti- inflammatory and analgesic efficacies of AP are entirely due to the presence of high contents of andrographolide present in it.
Osteoarthritis (OA), being the most prominent degenerative joint disease is affecting millions of elderly people worldwide. Although Andrographis paniculata is an ethnic medicine with a long history of being used as analgesic agent, no study using a monosodium iodoacetate (MIA) model has investigated its potential activities against OA. In this study, experimental OA was induced in rats with a knee injection of MIA, which represents the pathological characteristics of OA in humans. A. paniculata extract (APE) substantially reversed the loss of hind limb weight-bearing and the cartilage damage resulted from the OA induction in rats.
Additionally, the levels of serum pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α as well as the concentration of matrix metalloproteinases, including MMP-1, MMP-3, MMP-8, and MMP-13 were decreased by APE administration. Acetic acid-induced writhing responses in mice which quantitatively measure pain were significantly reduced by APE. In vitro, APE inhibited the generation of NO and downregulated the expression of IL-1β, IL-6, COX-2, and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The above results suggest the potential use APE as a therapeutic agent against OA.
Angelica dahurica(Fisch.ex Hoffm.)Benth. etHook.f. root extract
analgesic and anti-inflammatory effect of the aqueous extract of Angelica dahurica
Background: Angelica dahurica has been used in various clinical cases. Its taste is hot and its property is warm, dry and nonpoisonous. Its efficacy is to remove wind-damp, cure swelling and edema, exhaust pus, stop itching, rhinitis and leukorrhea.
Object: To test through experiment Angelica dahurica’s analgesic and anti-inflammatory efficacy.
Method: Inject acetic acid as a pain–inducing substance to the mice and measure visceral pain bywrithing reflex. Inject carrageenan that is an edema–inducing substance to the rat’s paw and measure volume of edema. Take thermal pain to mice with plantar test and measure paw withdrawal latency. Normal group is non Angelica dahurica-treated group and treated group is Angelica dahurica-treated group.
Results: In acetic acid-induced visceral model, treatment with Angelica dahurica suppressed writhing reflex significantlyand dose-dependently. In carrageenan-induced paw edema model, treatment with Angelica dahurica suppressed carrageenan-induced paw edema. In plantar test model, no significant effect on the withdrawal latency of thermal stimulation-induced nociception was observed.
Conclusion: Angelica dahurica has analgesic and anti-inflammatory efficacy.
Angelica pubescens Maxim.f.biserrata Shan et Yuan root extract
anti-inflammatory and analgesic activities from roots of Angelica pubescens
In the present study, we extracted Angelica pubescens (AP) with various solvents in order to find the bioactive constituents that demonstrated analgesic and anti-inflammatory effects. The results were obtained as follows: (1) Methanol-, chloroform-, and ethyl acetate-extracts effectively reduced the pain that was induced by 1% acetic acid and a hot plate. (2) Methanol-, chloroform-, and ethyl acetate-extracts reduced the edema that was induced by 3% formalin or 1.5% carrageenan. (3) Sixteen compounds have been isolated and identified from the roots of AP. Among these compounds, columbianadin, columbianetin acetate, bergapten, umbelliferone, and caffeic acid significantly demonstrated anti-inflammatory and analgesic activities at 10 mg/kg. However, only osthole and xanthotoxin revealed anti-inflammatory activity. Isoimperatorin only demonstrated an analgesic effect.
Antrodia camphorata extract
Ergostatrien-3β-ol (ST1), an active and major ingredient from Antrodia camphorata (AC) submerged whole broth was evaluated for the analgesic and anti-inflammatory effects. treatment of male imprinting control region (ICR) mice with ST1 (1, 5, and 10 mg/kg) significantly inhibited the numbers of acetic-acid-induced writhing response in 10 min. Also, our result showed that ST1 (10 mg/kg) significantly inhibited the formalin-induced pain in the late phase (p < 0.001). In the anti-inflammatory test, ST1 (10 mg/kg) decreased the paw edema at 4 and 5 h after λ-carrageenin (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue.
We also demonstrated that ST1 significantly attenuated the malondialdehyde (MDA) level in the edema paw at 5 h after Carr injection. ST1 (1, 5, and 10 mg/kg) decreased the nitric oxide (NO) levels on both the edema paw and serum level at 5 h after Carr injection. Also, ST1 (5 and 10 mg/kg) diminished the serum tumor necrosis factor (TNF-α) at 5 h after Carr injection. Western blotting revealed that ST1 (10 mg/kg) decreased Carr-induced inducible nitric oxide synthase (iNOS), and cycloxyclase (COX-2) expressions at 5 h in the edema paw. An intraperitoneal (ip) injection treatment with ST1 also diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory mechanisms of ST1 might be related to the decrease in the level of MDA, iNOS, and COX-2 in the edema paw via increasing the activities of CAT, SOD, and GPx in the liver through the suppression of TNF-α and NO.
Aquilaria sinensis(Lour.)Gilg extract
antinociceptive and anti-inflammatory activities of Aquilaria sinensis (Lour.) Gilg. leaves extract
Aim of the study: The analgesic and anti-inflammatory activities of the ethanol extract of Aquilaria sinensis (Lour.) Gilg. leaves were observed in various experimental models related to nociception and inflammation, so as to provide some evidence for its traditional use.
Materials and methods: Acetic acid-induced writhing and a hot plate test in mice were used to evaluate its analgesic activity. On the other hand, its anti-inflammatory activity was observed in xylene or carrageenan-induced edema, carboxymethylcellulose sodium (CMC-Na)-induced leukocyte migration in mice and lipopolysaccharide (LPS)-induced nitric oxide (NO) release from mouse peritoneal macrophages in vitro.
Results: The ethanol extract significantly inhibited acetic acid-induced writhing after single oral administration at doses of 424 and 848 mg extract/kg, and the response to the thermal stimulus in mice at the dose of 848 mg/kg. Meanwhile, the ethanol extract also remarkably lessened xylene-induced ear swelling, carrageenan-induced paw edema, and CMC-Na-induced leukocyte migration. Furthermore, the extract considerably reduced NO release from LPS-stimulated macrophages with IC50 of 80.4 mg/ml.
Conclusion: These findings suggest that Aquilaria sinensis (Lour.) Gilg. leaves extract present notable analgesic and anti-inflammatory activities, which support its folkloric use for some diseases related with painful and inflammatory conditions such as trauma etc.
Ardisia gigantifolia Stapf extract
Ardisia: health–promoting properties and toxicity of phytochemicals and extracts
Ardisia species (Myrsinaceae) are found throughout tropical and subtropical regions of the world. Traditional medicinal uses attributed to Ardisia include alleviation of liver cancer, swelling, rheumatism, earache, cough, fever, diarrhea, broken bones, dysmenorrhea, respiratory tract infections, traumatic injuries, inflammation, pain, snake and insect bites, birth complications and to improve general blood circulation, among others. Ardisia species are rich in polyphenols, triterpenoid saponins, isocoumarins, quinones and alkylphenols. A summary of the uses, potential health benefits, adverse reactions and important bioactive phytochemicals isolated from the Ardisia species is presented.
Future research needs to include more toxicological studies, more comprehensive chemical characterization of extracts, bioavailability, extract standardization, investigation of possible herb–drug interactions, plant improvement with regards to bioactivity and composition, and additional human and animal studies to confirm the health–promoting properties claimed for Ardisia species. The information presented here exemplifies the potential of Ardisia species as a source of chemotherapeutic, chemo-modulating and/or chemopreventive agents.
Artemisia absinthium
Nature has been a source of medicinal agents for thousands of years and has been isolated the number of modern drugs from natural resources. Artemisia absinthium used for a variety of medicinal purposes and therapeutic targets in all over the world, such as localized pains, contusion inflammation, anti-rheumatic, include fever reduction, digestive ailments and muscle pain. This study aimed to assess the anti-inflammatory and anti-nociceptive activity of essential oil and aqueous extract from Artemisia absinthium for the first time.
Chemical compositions of the essential oil were determined by GC/MS. The anti-inflammatory activity was evaluated by carrageenan-induced paw edema in mice. analgesic activity was assessed by acetic acid-induced writhing, formalin and hot plate tests in mice. Pretreatment with the essential oil (at the dose of 2, 4 and 8mg/kg) and aqueous extract (50, 100 and 200mg/kg) showed potential anti-inflammatory and anti-nociceptive effects to different level. The essential oil at 4 and 8 mg/kg significantly reduced carrageenan induced paw edema. The essential oil and aqueous extract produced significant decreased number of writhing in acetic acid-induced writhing model and increased the response latency in hot plate test after 30 min.
Both essential oil and aqueous extract significantly suppressed in a dose-dependent manner the nociceptive response in the formalin test, while the effect on the late phase was more pronounced. GC–MS analyses showed the presence of twenty components in essential oil. The essential oil and aqueous extract possesses excellent anti-inflammatory activity as well as antinociceptive properties especially peripheral analgesic.
Artemisia herba alba
Seeds and samples of stems from the two medicinal plants, Lactuca scariola and Artemisia absinthium respectively were extracted in absolute methanol to determine their analgesic and anti-inflammatory activity. The analgesic activity was assessed on intact mice by tail flick latency in tail immersion method. The anti-inflammatory activity was estimated volumetrically by measuring the mean increase in hind paw volume of rat with the help of plethysmometer. Acetylsalicylic acid in the dose of 300 mg/kg is used as standard drug. Both plant extracts were given in the doses of 300, 500 and 1000 mg/kg. Control group received 0.9% NaCI (saline) solution. All the doses administered orally. results showed that Lactuca had potent analgesic activity and Artemisia had significant analgesic and anti-inflammatory activity.
AsariRadix Et Rhizoma extract
Objective: To study the analgesic effects of aqueous extract from Asari Radix et Rhizoma (ARR) combined with Nimodipine and its mechanism.
Methods: Forty healthy male Wistar rats were r andomly divided into control, model, ARR, Nimodipine, and ARR+Nimodipine groups. Except the control group, the neuropathic pain models of rats were produced in the rest groups by the ligation of sciatic nerve. Rats in each group were ig administered for two weeks after operation. The aqueous extract (200 mg/kg) from ARR was given to rats in ARR group, Nimodipine (40 mg/kg) was given to rats in Nimodipine group, and the aqueous extract (200 mg/kg) from ARR was given to rats after 30 min administration of Nimodipine (40 mg/kg) in ARR+Nimodipine group, and physiological saline was given to rats in the control and model groups. Thermal paw withdrawal latency and mechanical paw withdrawal reflex threshold of rats in each group were measured on one day before operation and on the days 1, 3, 5, 9, and 14 after 30 min of administration.
Results: The thermal paw withdrawal latency and mechanical paw withdrawal reflex threshold of rats in each group were not significantly different before and after the operation (P>0.05). The thermal paw withdrawal latency and mechanical paw withdrawal reflex threshold of rats in the model group were significantly lower than those in the control group at various time points after the operation (P<0.05 and 0.01). The thermal paw withdrawal latency and mechanical paw withdrawal reflex threshold of rats in ARR and Nimodipine groups were significantly higher than those in the model group from the day 5 after the operation (P<0.05 and 0.01). The thermal paw withdrawal latency and mechanical paw withdrawal reflex threshold of rats in ARR+Nimodipine group were significantly higher than those in the model group from the day 3 after the operation (P<0.05 and 0.01), and were significantly higher than those of both in ARR and Nimodipine groups from the day 5 after the operation (P<0.05 and 0.01). analgesic effects of ARR+Nimodipine group were better than those of separate ARR and Nimodipine groups.
Conclusion: The aqueous extract from ARR combined with Nimodipine has the ideal analgesic effects.
Asarum sieboldii Miq.extract
The radix of Asarum sieboldii Miq. (AR) has been used to treat pain and inflammation in Korea. The present study was conducted to gain insights into the mechanism of actions regarding anti-nociceptive and anti-inflammatory activities of AR. Administration of methanol extract of AR caused dramatic anti-nociceptive effects based on acetic acid writhing and tail-flick assay. When naloxone (Nx) was pre-treated, AR extract failed to exert such anti-nociceptive effect in the tail-flick assays.
These results suggest that AR extract have opioid-like activity. It also exerted significant anti-inflammatory effects in the rat paw edema assay. AR extract caused inhibition in the bradykinin (BK)/histamine-mediated ileum contractions of guinea pig. Taken together, these results provide evidence that the methanol extract of AR exerts anti-nociceptive and anti-inflammatory effects by activating opioid receptor as well as by inhibiting bradykinin and histamine-mediated actions.
Astragali radix
pain relieving and protective effects of Astragalus hydroalcoholic extract in rat arthritis models
Objectives: The evaluation of the pharmacological profile of the dried 50% hydroalcoholic extract (50%HA) of Astragali radix in two different animal models of articular damage resembling osteoarthritis and rheumatoid arthritis.
Methods: Sodium monoiodoacetate (MIA) or complete Freund’s adjuvant (CFA) was intra-articular injected (day 0) in the rat tibiotarsal joint to induce damages mimicking osteoarthritis or rheumatoid arthritis. pain measurements (responses to non-noxious and noxious stimuli, spontaneous pain, articular pain) were assessed on days 7 and 14. On day 14, the tibiotarsal joints were explanted in order to measure the diameter and to assess histological evaluations. Furthermore, the plasmatic concentrations of inflammatory and anti-inflammatory cytokines were measured.
Results: A single administration of 50%HA (300 mg/kg per os) significantly reduced both MIA-induced pain and CFA-induced pain (78% and 96% pain relief, respectively). The repeated administration prevented the development of hypersensitivity on day 14. The haematoxylin/eosin staining revealed that 50% HA attenuated joint alterations in MIA-injected rats, and furthermore, the joint inflammatory infiltrate was reduced in both models (by about 50%). In CFA-treated rats, 50%HA lowered the plasmatic levels of the pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α as well as the joint diameter.
Conclusion: The 50% hydroalcoholic extract of Astragali radix is a valuable candidate for the adjuvant treatment of articular diseases.
Aucklandia lappa Decne. root extract
Osteoarthritis (OA) is an age-related joint disease and one of the most common degenerative bone diseases among elderly people. The currently used therapeutic strategies relying on nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for OA are often associated with gastrointestinal, cardiovascular, and kidney disorders, despite being proven effective. Aucklandia lappa is a well-known traditional medicine. The root of A. lappa root has several bioactive compounds and has been in use as a natural remedy for bone diseases and other health conditions.
We evaluated the A. lappa root extracts on OA progression as a natural therapeutic agent. A. lappa substantially reduced writhing numbers in mice induced with acetic acid. Monosodium iodoacetate (MIA) was injected into the rats through their knee joints of rats to induce experimental OA, which shows similar pathological characteristics to OA in human. A. lappa substantially reduced the MIA-induced weight-bearing of hind limb and reversed the cartilage erosion in MIA rats. IL-1β, a representative inflammatory mediator in OA, was also markedly decreased by A. lappa in the serum of MIA rats. In vitro, A. lappa lowered the secretion of NO and suppressed the IL-1β, COX-2, IL-6, and iNOS production in RAW264.7 macrophages activated with LPS. Based on its analgesic and anti-inflammatory effects, A. lappa could be a potential remedial agent against OA.
Averrhoa carambola L. extract
Objectives: This study was aimed to investigate the analgesic and anti-inflammatory activities of crude methanolic extract Averrhoa bilimbi leaves.
Materials and Methods: Methanolic extracts of Averrhoa bilimbi leaves with different concentration were tested for analgesic activity in mouse model by acetic acid induced writhing and anti-inflammatory effect was tested by carrageenan induced paw edema model
Results: The extract, at 400 mg/kg, showed higher analgesic activity (67.51%) against acetic acid induced pain in mice while the standard reference drug Diclofenac sodium exhibited 64.33% activity at 10 mg/kg dose. The anti-inflammatory effect of the extract was comparable to reference drug Ibuprofen and the effect was sustained for 2-4 hr.
Conclusion: Methanolic extractof Averrhoa bilimbi leaves have moderate analgesic and anti-inflammatory properties.
Borassus flabellifer L.(Arecaceae) flowers
Analgesic and antipyretic effects of ethanolic extract of male flowers (inflorescences) of Borassus flabellifer L. (Arecaceae) were investigated at doses 150mg/kg b.w. and 300mg/kg b.w. using acetic-acid induced writhing, hot-plate, tail-clip, formalin and yeast-induced pyrexia tests. oral administration Borassus flabellifer ethanolic extract (BFEE) produced significant (P<0.0001) reduction in no. of writhes induced by acetic-acid.
Moreover, in hot-plate test, BFEE significantly (P<0.0001) raised the pain threshold at different time of observation (0-60min) in comparison with control. In tail-clip test also the extract caused a significant (P<0.0001) inhibition of pain at both the doses used. There was a significant dose-dependent inhibition of both phases of the formalin induced pain response in mice. Tested on yeast-induced pyrexia in rats, BFEE significantly (P<0.0001) reversed hyperthermia at either dose. The results of pharmacological tests performed in the present study suggest that BFEE possesses potent analgesic and antipyretic effects.
Boswellia carterli Birdw extract
anti-inflammatory and analgesic activity of different fractions of Boswellia serrata
The study was designed to investigate the anti-inflammatory and analgesic effect of different fractions of Boswellia serrata. The effect of different fractions of Boswellia serrata were studied using carrageenan induced paw edema, acetic acid induced writhing response, formalin induced pain, hot plate and tail flick method for studying anti-inflammatory and analgesic activity, respectively. The different fractions of B. serrata, essential oil (10 ml/kg), gum (100 mg/kg, resin (100 mg/kg) oleo-resin (100 mg/kg) and oleo- gum-resin (100 mg/kg) significantly reduces carrageenan induced inflammation in rats and shows analgesic activity, as determined by acetic acid induced writhing response, formalin induced pain, hot plate and tail flick method.
The different fractions of B. serrata showed prompt anti-inflammatory and analgesic activity due to the inhibition of 5-lipoxygenase enzyme.
Boswellia serrata resin (Frankincense)
natural anti-inflammatory agents for pain relief
The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions.
This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use.
Caesalpinia sappanL. extract
Sappan wood (Caesalpinia sappan L.) is used as an analgesic and antipyretic by the Indonesian people, empirically. The aim of this study was to determine the analgesic and antipyretic activity of ethanolic extract of sapan wood leaves in Webster mice as experimental animals. The writhing method was used to determine the analgesic activity in acetic acid-induced mice with mefenamic acid as a positive control. The temperature reduction method was used to determine the antipyretic activity in yeast-induced mice with paracetamol as a positive control. One-way ANOVA was conducted for statistical analysis, followed by Tukey-Kramer post hoc test. phytochemical screening showed that sappan wood contains alkaloids, flavonoids, saponins, monoterpenoids, and sesquiterpenoids. The optimum dose of analgesic and antipyretic activity was 6.3 mg and 8.4 mg/20 g BW of mice, respectively.
The conclusion was ethanolic extract of sappan wood leaves has analgesic and antipyretic activities.
Callicarpa formosana Rolfe extract
Ethnopharmacological relevance: Callicarpa L. (Verbenaceae) has been used for centuries in Traditional Chinese medicine (TCM) for the prevention and treatment of a wide number of health disorders such as inflammation, rheumatism, hematuria, fracture, hematemesis, menoxenia, gastrointestinal bleeding, scrofula, etc.
Aims of the review: To assess the scientific evidence for therapeutic Callicarpa in TCM and to identify future research needs.
Methods: The available information on the ethnopharmacological uses in Chinese medicine, phytochemistry, pharmacology and clinical practice of Callicarpa species was collected via a library and electronic search (PubMed, ScienceDirect, Google Scholar and CNKI).
Results: A variety of ethnomedical use of Callicarpa has been recorded in many ancient Chinese books. phytochemical investigation of this genus has resulted in identification of more than 200 chemical constituents, among which diterpenes, triterpenoids and flavonoids are the predominant groups. The isolates and crude extract have exhibited a wide spectrum of in vitro and in vivo pharmacological effects involving anti-inflammatory, hemostatic, neuroprotective, anti-amnesic, antitubercular, antioxidant, antimicrobial and analgesic activities. Preparations containing Callicarpa species exerted good efficacy on clinical applications of gynecological inflammation, internal and external hemorrhage as well as acne vulgaris and chronic pharyngitis, etc. From the toxicity perspective, only three Callicarpa species have been assessed.
Conclusion: Pharmacological results have validated the use of Callicarpa species in the traditional medicine. As literature demonstrated, terpenoids and flavonoids are perhaps responsible for most of the activities shown by the plants of this genus. However, the detailed active compounds and the underlying mechanisms remain a work in progress. In addition, more attention should be paid to C. nudiflora as well as the domain of rheumatism.
Campsis grandiflora extract
In vitro and in vivo evaluation of pharmacological potentials of Campsis radicans L
Background: Campsis radicans L. is a flowering plant in Bangladesh, traditionally used for the treatment of several human diseases. In this study, in vitro antioxidant, thrombolytic, membrane stabilizing and in vivo analgesic, hypoglycemic, anti-diarrheal and CNS antidepressant activities of organic soluble fractions of crude methanol extract of C. radicans leaf were investigated using appropriate experimental models.
Methods: The leaves of C. radicans were collected, authenticated, dried and extracted with methanol at room temperature for 30 days. The concentrated methanol extract was partitioned to petroleum-ether (PESF), dichloromethane (DMSF) and ethyl acetate (EASF) soluble fractions. The antioxidant activity of these fractions was determined by DPPH free radical scavenging method. Total phenolic content was determined by the Folin-Ciocalteau’s spectrophotometric method. The thrombolytic activity was assessed by measuring clot lysis ability whereas the membrane stabilizing activity was evaluated by heat- and hypotonic solution-induced hemolysis assay. Tail immersion procedure and acetic acid- induced writhing model were used to measure the analgesic activity of C. radicans. The hypoglycemic, anti-diarrheal and CNS antidepressant activities were determined by oral glucose tolerance test, castor oil-induced diarrheal model and thiopental-sodium induced sleeping time test in mice, respectively.
Results: All the organic soluble fractions of C. radicans contained phenolic compounds varying from 6.38 to 60.13 mg of GAE/gm of extractive, while in DPPH assay, EASF showed the highest free radical scavenging activity with IC50 is 4.69 μg/ml. The PESF exhibited highest thrombolytic activity (57.14% clot lysis) and the DMSF showed maximum 53.95% inhibition of heat-induced hemolysis of human RBCs. In both tail immersion and acetic acid induced writhing models, the PESF, DMSF, EASF at the doses of 200 and 400 mg/kg body weight, induced a significant (P < 0.001) decrease in the painful sensation in mice. substantial (P < 0.05) anti-hyperglycemic activity of test samples was found in mice loaded with glucose at the same doses mentioned earlier. Castor oil induced diarrheal test of the plant extractives has shown significant effect in comparison to control group. In CNS antidepressant activity assay, the test samples were able to reduce the duration of sleep in mice caused by thiopental administration.
Conclusion: All these findings revealed that C. radicans possess significant antioxidant, thrombolytic, membrane stabilizing, analgesic, hypoglycemic, anti-diarrheal and CNS antidepressant activities.
capsaicin
Pain from oral mucositis afflicts from 40% to 70% of patients receiving chemotherapy or radiation therapy. Current methods of clinical pain management (for example, topical anesthetics, systemic analgesics) have limited success. In a pilot study, we examined the ability of oral capsaicin to provide temporary relief of oral mucositis pain. Capsaicin, the active ingredient in chili peppers, desensitizes some neurons and has provided moderate pain relief when applied to the skin surface. oral capsaicin in a candy (taffy) vehicle produced substantial pain reduction in II patients with oral mucositis pain from cancer therapy.
However, this pain relief was not complete for most patients and was only temporary. Additional research is needed to fully utilize the properties of capsaicin desensitization and thus optimize analgesia.
Cardiospermum halicacabum L. extract
Background: One of the major health problems among elderly is osteoarthritis which leaves them suffering from chronic joint pain. Prescription of pharmacological measures such as analgesics to treat the joint pain causes many adverse effects and non-compliance. This study attempts to inquire the use of herb as a pain–relieving measure among elderly as it does not produce any side effects and easily available at affordable costs. Objective: To evaluate the effectiveness of Cardiospermum halicacabum leaves Soup on chronic Knee pain among elderly population
Method: Pre-experimental study was conducted among 30 elderly persons residing at Dharmapuri, South India. Pre-test level of chronic knee pain among elderly was assessed through Numeric pain Intensity Rating Scale. 100ml of freshly prepared Cardiospermum halicacabum leaves soup was given to the participants once in a day for 21 days and then post-test level of chronic knee pain was assessed.
Results: There was significant difference (p<0.05) found between mean pre-test (7.6 ± 0.83) and post-test (2.73 ± 1.04) pain score. The pretest level of pain has significant association (p<0.05) with the occupation, type of work and BMI.
Carthamus tinctorius L flower extract
Ethnopharmacological relevance: Safflower (Carthamus tinctorius L.) has been long used both in the traditional system and folk medicine as an analgesic anti-inflammatory agent in China. The aim of the study was to evaluate the antinociceptive and anti-inflammatory activities of hydroalcoholic extract (HE) and two isolated kaempferol glycosides of Carthamus tinctorius L. to provide experimental evidence for its traditional use.
Materials and methods: antinociceptive effects of HE, kaempferol 3-O-rutinoside (K-3-R) and kaempferol 3-O-glucoside (K-3-G) were assessed in mice using the acetic acid-induced writhing test, formalin test and cinnamaldehyde test. The anti-inflammatory effects of HE, K-3-R and K-3-G were determined in two animal models: carrageenan-induced paw edema and xylene-induced ear edema.
Results: The HPLC analysis showed the presence of K-3-R and K-3-G in Carthamus tinctorius L. HE (500 and 1000 mg/kg) as well as K-3-R and K-3-G (150, 300 and 600 mg/kg) produced significant inhibition on nociception induced by acetic acid and formalin. oral treatment of HE, K-3-R and K-3-G at all doses significantly reduced both the nociceptive response and cinnamaldehyde-induced paw edema, effect that was superior to aspirin. In anti-inflammatory tests, HE and K-3-G significantly inhibited the paw edema during the both phases of carrageenan-induced inflammation while K-3-G suppressed the late phase inflammation only. HE (400 and 800 mg/kg) and K-3-G (200, 400, 800 mg/kg) produced significant dose-dependent inhibition of xylene-induced ear edema development. K-3-R only suppressed ear edema formation at a high dose (800 mg/kg).
Conclusion: These results demonstrate that Carthamus tinctorius L. extract possess remarkable antinociceptive and anti-inflammatory activities which may be due to K-3-R and K-3-G at least in part, supporting the folkloric usage of the plant to treat various inflammatory and pain diseases.
Chelidonium majus extract
The aim of the study was to evaluate analgesic activity (“hot plate” test), anti-inflammatory activity (carrageenan-induced paw edema) and locomotor activity in rats under the influence of three fractions of Chelidonium majus herb extract: full water extract (FWE), protein enriched fraction (PEF), and non-protein fraction (NPF). effects of the fractions on the level of chosen cytokines and their mRNA levels were also assessed using lipopolysaccharide (LPS) administration as a proinflammatory cue. All fractions and diclofenac did not affect the locomotor activity of rats in comparison with the control group. FWE and PEF three hours after administration showed statistically significant analgesic activities comparable to morphine (p < 0.05). A slight reduction in rat paw edema was observed after three (comparable with diclofenac) and six hours in the NPF group. FWE revealed a statistically significant pro-inflammatory effect after three hours in comparison with the control group. Peripheral IL-1 and IL-4 cytokine concentrations were reduced under FWE and NPF, PEF fractions. The combination of FWE, PEF and NPF together with LPS showed only the effects of LPS.
We suggest that protein enriched fraction (PEF) produced centrally mediated (morphine-like) analgesic action, whereas the anti-inflammatory potential was shown only after LPS-induced inflammation. The precise mechanisms involved in the production of anti-nociceptive and anti-inflammatory responses of studied fractions are not completely understood, but they may be caused rather by the presence of protein more than alkaloids-enriched fraction. This fraction of the extract could be used as an alternative therapy for the prevention of inflammatory-related diseases in the future, but further studies are needed.
Cimifugin, from root of Saposhnikovia divaricata
analgesic components of Saposhnikovia Root (Saposhnikovia divaricata)
By activity-oriented separation using the writhing method in mice, the analgesic components of Saposhnikovia root (Saposhnikovia divaricata Schischkin; Umbelliferae) were identified to be chromones, coumarins, polyacetylenes and 1-acylglycerols. Two new components, divaricatol and (3’S)-hydroxydeltoin, were also isolated. The most potent analgesia was observed in chromones such as divaricatol, ledebouriellol and hamaudol, which inhibited writhing inhibition at an oral dose of 1 mg/kg in mice. Acylglycerols also showed inhibition significantly at a dose of 5 mg/kg.
In some pharmacological tests using sec-O-glucosylhamaudol, the compound showed analgesia by the tail pressure and the Randall & Selitto methods, and its writhing inhibition was not reversed by naloxone.
Saposhnikovia divaricata Schischkin has been used in traditional medicine to treat pain, inflammation, and arthritis. The aim of this study was to investigate the anti-inflammatory and Antiosteoarthritis activities of Saposhnikovia divaricata extract (SDE). The anti-inflammatory effect of SDE was evaluated in vitro in lipopolysaccharide- (LPS-) treated RAW 264.7 cells. The antiosteoarthritic effect of SDE was investigated in an in vivo rat model of monosodium iodoacetate- (MIA-) induced osteoarthritis (OA) in which rats were treated orally with SDE (200 mg/kg) for 28 days.
The effects of SDE were assessed in vivo by histopathological analysis and by measuring weight-bearing distribution, cytokine serum levels, and joint tissue inflammation-related gene expression. SDE showed anti-inflammatory activity by inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in LPS-induced RAW 264.7 cells. In addition, SDE promoted recovery of hind limb weight-bearing, inhibited the production of proinflammatory cytokines and mediators, and protected cartilage and subchondral bone tissue in the OA rat model. Therefore, SDE is a potential therapeutic agent for OA and/or associated symptoms.
Background: Cimifugin is one of the components of the root of Saposhnikovia divaricata. The extract derived from S. divaricata is traditionally used as an analgesic. This study was conducted to evaluate the analgesic effect of intrathecal cimifugin in the formalin test.
Methods: Male Sprague–Dawley rats (n = 20) were randomized into four groups for intrathecal administration of 70% dimethylsulfoxide and various doses of cimifugin (100 μg, 300 μg, and 1,000 μg). The typical flinch response after the injection of 5% formalin into the hind paw was assessed in two distinct phases: phase 1 until 10 min, and phase 2 from 10 min to 60 min. ED50 values were calculated via linear regression.
Results: Intrathecal cimifugin significantly reduced the flinch response in both phases of the formalin test. significant antinociceptive effects of cimifugin were found with the dose of 300 μg in phase 1 and the dose of 100 μg in phase 2. The ED50 value (95% confidence intervals) of intrathecal cimifugin was 696.1 (360.8–1,342.8) μg during phase 1 and 1,242.8 (42.0–48,292.5) μg during phase 2.
Conclusion: Intrathecal cimifugin has an antinociceptive effect against formalin-induced pain. Cimifugin has an anti-inflammatory effect at low concentrations, and non-inflammatory analgesic effect at higher concentrations.
Cinnamomum cassia Pres peel extract
The essential oil from the twigs of Cinnamomum cassia Presl alleviates pain and inflammation in mice
Ethnopharmacological relevance: Cinnamomum cassia Presl (Lauraceae) can be found southern China and its bark is commonly used for centuries as ingredient in food and cosmetic industry. The twigs of Cinnamomum cassia Presl is popularly used in China to treat inflammatory processes, pain, menstrual disorders, hypertension, fever etc. The aim of this study is to evaluate the antinociceptive and anti-inflammatory properties of the essential oil (EO) from the twigs of Cinnamomum cassia Presl.
Material and methods: The chemical characterization of the EO was performed by gas chromatography coupled with mass spectrometry (GC-MS). The EO doses of 15, 30, and 60 mg/kg were employed in the biological assays. The antinociceptive effects of the EO were evaluated using the models of acetic acid-induced writhing, oxytocin-induced writhing, and formalin and complete Freund’s adjuvant (CFA) –induced overt pain tests. we also investigated the effect of the EO in pain intensity to a mechanical stimulus (mechanical hyperalgesia) after carrageenan by using an electronic version of von Frey filaments. Evaluation of anti-inflammatory activity was based on paw edema induced by carrageenan (300 µg/25 µL/paw) in mice. The levels of cytokines, NO, and PGE2 in paw skin tissue were determined according to instructions. COX-2 and iNOS proteins in paw skin tissue were assessed by Western Blot.
Results: The EO (15, 30, and 60 mg/kg) reduced the number of abdominal writhings induced by acetic acid with inhibition of 38.0%, 55.4% and 58.7%, respectively. The EO (15, 30, and 60 mg/kg) also reduced the number of abdominal writhings induced by oxytocin with inhibition of 27.3%, 51.7% and 69.0%, respectively. The EO significant inhibited the inflammatory (second phase: 10–30 min) phase of the formalin-induced paw flinching and licking at the doses of 15, 30, and 60 mg/kg. The EO at the tested doses of 15, 30, and 60 mg/kg showed inhibited CFA-induced paw flinching and licking. The EO (15, 30, and 60 mg/kg) also inhibited carrageenan-induced mechanical hyperalgesia and paw edema. It also decreased the levels of cytokines (TNF-α, and IL-1β), NO, and PGE2 in carrageenan-induced mice paw skin tissue. Moreover, Western blot analysis showed that COX-2 and iNOS expressions in paw skin tissue of mice were significantly reduced.
Conclusion: These results demonstrate that the antinociceptive and anti-inflammatory properties of the EO from the twigs of Cinnamomum cassia Presl, corroborating its use in folk medicine.
Cinnamon Zeylanicum
antinociceptive effect Of Cinnamon extract On Formalin induced pain In Rat
Since time memorial, herbal medicine has played an important role for relief of various symptoms including pain relief. Many researchers have focused on the curative as well as antinociceptive effects of herbal extracts. Cinnamon Zeylanicum has long been prescribed in traditional medicine for the treatment of inflammatory-related diseases such as rheumatisms, bronchitis and muscle pains. However, there is little if any scientific research indicating this effect.Methods: This experimental study was carried out in Shaheed Sadoughi medical School on 25 Wistar Rats (200-300grams) randomly divided into 5 groups. In this study, the analgesic effect of intraperitoneal administration of hydro-alcoholic Cinnamon extract in different doses (50,100,500mg/kg) was assessed by using Formalin Test (for chronic pain) during 1hr. post Formalin injection.results: Our results indicated that cinnamon extract in high dose (500mg/kg) decreased the chronic pain intensity in the 2nd phase of formalin test.
This analgesic effect was significant (P<0.001) as compared with sham group, but the lower doses (50 &100mg/kg) of cinnamon extract did not show any analgesic effect on chronic pain in Formalin Test.conclusion: Data from this study confirms the analgesic effect of high doses (500mg/kg) of cinnamon extract on chronic pain in Formalin Test which may be due to anti-inflammatory effect of this plant material.
Cissampelos pareira
Cissus quadrangularis
analgesic, anti-inflammatory and venotonic effects of Cissus quadrangularis Linn.
Cissus quadrangularis, a medicinal plant indigenous to Asia and Africa, is used for many ailments, especially for the treatment of hemorrhoid. The effects associated with hemorrhoid, i.e. analgesic and anti-inflammatory activities as well as the venotonic effect of the methanol extract of C. quadrangularis (CQ) were assessed in comparison with reference drugs. In the analgesic test, CQ provoked a significant reduction of the number of writhes in acetic acid-induced writhing response in mice. CQ also significantly reduced the licking time in both phases of the formalin test. The results suggest peripheral and central analgesic activity of CQ. In acute phase of inflammation CQ elicited the inhibitory effect on the edema formation of the rats’ ear induced by ethyl phenylpropiolate as well as on the formation of the paw edema in rats induced by both carrageenin and arachidonic acid. It is likely that CQ is a dual inhibitor of arachidonic acid metabolism.
In addition, CQ exerted venotonic effect on isolated human umbilical vein similarly to the mixture of bioflavonoids, i.e. 90% diosmin and 10% hesperidin. The results obtained confirmed the traditional use of C. quadrangularis for the treatment of pain and inflammation associated with hemorrhoid as well as reducing the size of hemorrhoids.
Clematis chinensis Osbeck. extract
Aim: Clematis terniflora DC. has been widely used as a traditional Chinese medicine for the treatment of tonsillitis, rheumatoid arthritis, and prostatitis. Despite its widespread use in China, there are currently no studies systematically examined its therapeutic effects and mechanism of action. As such, the present study was conducted to evaluate the anti-inflammatory, antinociceptive, and immunomodulatory effects of C. terniflora DC. using rodent and cellular models.
Methods: The anti-inflammatory properties of the 70% ethanol eluted fraction of the 70% ethanol extract of C. terniflora DC. (EECTD) were evaluated using the xylene-induced ear swelling test, the carrageenan-induced edema model, and the cotton pellet granuloma method. Its antinociceptive activities were determined using both the acetic acid-induced writhing test and the hot plate assay. In parallel, we conducted an in vitro assay in LPS-induced RAW264.7 cells to examine the anti-inflammatory effects of EECTD and its purified form, aurantiamide acetate (AA) on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2) release.
Results: EECTD (300 mg/kg) significantly reduced the number of writhing, extended the pain response latency, and suppressed xylene-induced ear swelling. Each EECTD treatment group also had significant inhibition of cotton granulation formation in addition to reduced carrageenan-induced paw edema. EECTD was also shown to alleviate signs of inflammation in histopathological paw sections. However, it had a less noticeable effect on mouse ear swelling in the delayed type hypersensitivity test. A purified compound was isolated from EECTD and its structure was identified as AA. In vitro experimental results showed that both EECTD and AA were able to significantly inhibit the release of pro-inflammatory cytokines NO and PGE2 on LPS-induced RAW264.7 cells.
Conclusion: These results suggest that EECTD has significant anti-inflammatory and antinociceptive activities, partially related to one of the active substances identified as AA. We hypothesize that these effects are related to its ability to inhibit the production of cytokines NO and PGE2. However, further work will be needed to determine its exact mechanism of action.
collybolide, Collybia maculata
Pain remains a very pervasive problem throughout medicine. Classical pain management is achieved through the use of opiates belonging to the mu opioid receptor (MOR) class, which have significant side effects that hinder their utility. Pharmacologists have been trying to develop opioids devoid of side effects since the isolation of morphine from papaver somniferum, more commonly known as opium by Sertürner in 1804. The natural products salvinorin A, mitragynine, and collybolide represent three nonmorphinan natural product-based targets, which are potent selective agonists of opioid receptors, and emerging next-generation analgesics. In this work, we review the phytochemistry and medicinal chemistry efforts on these templates and their effects on affinity, selectivity, analgesic actions, and a myriad of other opioid–receptor-related behavioral effects.
Collybolide is a novel biased agonist of κ-opioid receptors with potent antipruritic activity
Conolidine; an indole alkaloid derived from bark of Tabernaemontana divaricate
Conolidine: A novel plant extract for chronic pain
Pain, the most common symptom reported among patients in the primary care setting, is complex to manage. opioids are among the most potent analgesics agents for managing pain. Since the mid-1990s, the number of opioid prescriptions for the management of chronic non-cancer pain (CNCP) has increased by more than 400%, and this increased availability has significantly contributed to opioid diversion, overdose, tolerance, dependence, and addiction. Despite the questionable effectiveness of opioids in managing CNCP and their high rates of side effects, the absence of available alternative medications and their clinical limitations and slower onset of action has led to an overreliance on opioids. Conolidine is an indole alkaloid derived from the bark of the tropical flowering shrub Tabernaemontana divaricate used in traditional Chinese, Ayurvedic, and Thai medicine. Conolidine could represent the beginning of a new era of chronic pain management.
It is now being investigated for its effects on the atypical chemokine receptor (ACK3). In a rat model, it was found that a competitor molecule binding to ACKR3 resulted in inhibition of ACKR3’s inhibitory activity, causing an overall increase in opiate receptor activity. Although the identification of conolidine as a potential novel analgesic agent provides an additional avenue to address the opioid crisis and manage CNCP, further studies are necessary to understand its mechanism of action and utility and efficacy in managing CNCP.
Conus striatus venom
Conus striatus venom exhibits non-hepatotoxic and non-nephrotoxic potent analgesic activity in mice
Constant research into the pharmaceutical properties of marine natural products has led to the discovery of many potentially active agents considered worthy of medical applications. Genus Conus, which approximately comprises 700 species, is currently under every researcher’s interest because of the conopeptides in their crude venom. Conopeptides have a wide range of pharmacological classes and properties. This research focused on the crude venom of Conus striatus to assess its analgesic activity, mutagenicity, nephrotoxicity, and hepatotoxicity in mice. The crude venom was extracted from the conus snails and the protein concentration was determined using Bradford’s method. The analgesic activity of the venom was determined using the hot-plate method and standard IFCC method was used to determine the alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Evaluation of mutagenicity was done using micronucleus assay and the nephrotoxicity of the venom was determined using Kidney Coefficient and serum creatinine concentration. The maximum tolerable dose (MTD) of the crude venom was found to be 75 ppm. The venom exhibited potent analgesic activity even higher than the positive control (Ibuprofen). most of the analgesic drugs can usually impact damage in the liver and kidneys. However, AST and ALT results revealed that the venom has no adverse effects on the liver. Although the venom increased the incidence of micronucleated polychromatic erythrocytes, making it mutagenic, with MTD concentration’s mutagenicity comparable to the positive control methyl methanesulfonate (MMS). The kidney coefficients, on the other hand, showed no significant difference between the treated groups and that of the untreated group. The serum creatinine also showed a concentration-dependent increase; with MTD treated mice got the highest creatinine concentration.
However, MTD/2 and MTD/4 showed no significant difference in creatinine levels with respect to the untreated groups. Hence, the nephrotoxicity of the venom was only evident when used at higher concentration. The venom exhibited potent analgesic activity indicated that the C. striatus crude venom extract could have a potential therapeutic component as analgesic drugs that displayed no hepatic damage. This study also suggests that for this venom to be utilized for future medical applications, their usage must be regulated and properly monitored to avoid nephrotoxic effect.
Corydalis yanhusuo
The analgesic properties of Corydalis yanhusuo
Corydalis yanhusuo extract (YHS) has been used for centuries across Asia for pain relief. The extract is made up of more than 160 compounds and has been identified as alkaloids, organic acids, volatile oils, amino acids, alcohols, and sugars. However, the most crucial biological active constituents of YHS are alkaloids; more than 80 have been isolated and identified. This review paper aims to provide a comprehensive review of the phytochemical and pharmacological effects of these alkaloids that have significant ties to analgesia.
Curcuma alismatifolia
Evaluation of analgesic and antioxidant potential of the leaves of Curcuma alismatifolia
In the present study, the antioxidant and analgesic potential of the 80% methanol extract of the leaves of Curcuma alismatifolia Gangnep was evaluated. The extract was investigated for its antioxidant activity using lipid peroxidation, total antioxidant capacity and reducing power assays. The extract showed significant antioxidant activities in lipid peroxidation assay compared to the standard antioxidant in a dose dependent manner. In lipid peroxidation assay, the IC50 value was found to be 122.43μg/mL while the IC50 value for the reference ascorbic acid was 147.87μg/ml.
Moreover, Curcuma alismatifolia extract showed strong total antioxidant capacity and good reducing power. The analgesic activity was evaluated for its central and peripheral pharmacological actions using tail immersion method and acetic acid-induced writhing test in mice respectively. The extract, at the dose of 250 and 500 mg/kg, produced a significant (p < 0.05-0.001) increase in pain threshold in tail immersion methods in a dose dependent manner. In acetic acid-induced writhing test the extract, at a dose of 500 mg/kg, showed a maximum of 60.5% inhibition (p < 0.001) of writhing reaction compared to the reference drug diclofenac-sodium (75.0%). All experimental results suggest the use of this plant for the treatment of pain and inflammatory disorder.
Curcuma longaL. root extract
Turmeric (Curcuma longa) and its constituent, curcumin, have been used for their therapeutic properties for a long time. most of the medicinal impacts of turmeric and curcumin might be attributed to their anti-inflammatory, antinociceptive, and antioxidant effects. In the present review, the preventive and therapeutic potentials of turmeric and its active constituent, curcumin, on inflammatory disorders and pain as well as patents related to their analgesic and anti-inflammatory effects, have been summarized to highlight their value on human health.
A literature review was accomplished in Google Scholar, PubMed, Scopus, Google Patent, Patentscope, and US Patent. Several documents and patents disclosed the significance of turmeric and curcumin to apply in several therapeutic, medicinal, and pharmaceutical fields. These phytocompounds could be applied as a supplementary therapy in phytotherapy, inflammatory disorders such as arthritis, inflammatory bowel diseases, osteoarthritis, psoriasis, dermatitis, and different types of pain including neuropathic pain. However, because of inadequate clinical trials, further high-quality studies are needed to firmly establish the clinical efficacy of the plant. Consistent with the human tendency to the usage of phytocompounds rather than synthetic drugs, particular consideration must be dedicated to bond the worth of turmeric and curcumin from basic sciences to clinical applications.
Curcumae Radix extract
Background: Curcumae blood Radix (Yujin) has been widely used to treat Qi stagnation and stasis in TCM. According to the Chinese Pharmacopoeia, the tuberous roots of Curcuma longed L. (i.e., Huangsiyujin, HSYJ) is one of the major species of Yujin. According to the processing theory of TCM, stir-frying HSYJ with vinegar might strengthen the effect of dispersing stagnated hepatoqi to relieve pain, and stir-frying HSYJ with wine might strengthen the effect of promoting blood circulation in order to remove blood stasis. However, the mechanism for the enhancement of clinical efficacy by processing is unclear.
Aim/Hypothesis: This study was aimed at evaluating the effect of different processed products of HSYJ on chemical constituents and pain-related substances to explore underlying mechanisms of HSYJ in treating pain caused by Qi stagnation and blood stasis.
Methods: The effects of different processing methods on the paste yield of water decoction were analyzed, and the content of the main constituents were detected by HPLC. A rat model of Qi stagnation and blood stasis was established by tail clamp stimulation combined with subcutaneous adrenaline injection. After treatment and intervention with HSYJ and its processed products, β-endorphin (β-EP) and 5-hydroxytryptamine (5-HT) were measured by ELISA, and the expression of c-fos was evaluated by immunohistochemistry.
Results: After stir-frying with vinegar or wine, the extract yield and curcumin content increased. Compared with model group, raw HSYJ could significantly improve the abnormality of 5-HT in plasma (P < 0.05) and β-EP in brain (P < 0.01). Stir-frying HSYJ with vinegar or wine could significantly improve the abnormality of 5-HT in plasma, β-EP in brain, and the expression of c-fos (P < 0.01). Stir-frying HSYJ with vinegar could also significantly increase the level of β-EP in plasma (P < 0.05).
Conclusion: These results showed that different processing methods have certain effects on the chemical constituents of HSYJ, mainly in increasing the decoction rate and curcumin content. HSYJ and its processed products can reduce 5-HT levels, increase β-EP levels, and inhibit the expression of c-fos in model rats. The effects of stir-frying HSYJ with vinegar on β-EP levels in plasma was superior to others.
curcumin
Purpose To determine whether supplementation with turmeric or curcumin extract effects pain and physical function in individuals with knee osteoarthritis (OA). Second, we investigated the therapeutic response (pain and function) of turmeric compared with non-steroidal anti-inflammatory drugs (NSAIDs).
Methods A search was conducted in MEDLINE, Embase, CINAHL and Cochrane Review. Inclusion criteria included randomised controlled trials reporting pain and physical function in humans with knee OA comparing turmeric therapy with NSAIDs or no therapy. Two reviewers screened 5273 abstracts. Risk of bias and quality were assessed via Cochrane Collaboration tool and CONSORT (Consolidated Standards of Reporting Trials) 2010, respectively.
Results: Ten studies were included in the final analysis. Eight had high methodological quality and two were categorised as good with a mean CONSORT quality score of 21.1. Nine studies had adequate sequence generation and six had adequate allocation concealment. Participants and outcome assessors were blinded in eight studies. Three of the studies compared turmeric therapy to NSAIDs. All 10 studies showed improvement in pain and function from baseline with turmeric therapy (p≤0.05). In three studies comparing turmeric to NSAIDs, there were no differences in outcome scores (p>0.05). In all studies there were no significant adverse events in the turmeric therapy group.
Conclusion: Compared with placebo, there appears to be a benefit of turmeric on knee OA pain and function. Based on a small number of studies the effects are similar to that of NSAIDs. Variables such as optimal dosing, frequency and formulation remain unclear at this time.
Daemonorops draco Bl.extract
Dragon’s blood: Botany, chemistry and therapeutic uses
Dragon’s blood is one of the renowned traditional medicines used in different cultures of world. It has got several therapeutic uses: haemostatic, antidiarrhetic, antiulcer, antimicrobial, antiviral, wound healing, antitumor, anti-inflammatory, antioxidant, etc. Besides these medicinal applications, it is used as a coloring material, varnish and also has got applications in folk magic. These red saps and resins are derived from a number of disparate taxa. Despite its wide uses, little research has been done to know about its true source, quality control and clinical applications.
In this review, we have tried to overview different sources of Dragon’s blood, its source wise chemical constituents and therapeutic uses. As well as, a little attempt has been done to review the techniques used for its quality control and safety.
Dalbergia sissoo
analgesic and antipyretic activities of alcoholic extracts of Dalbergia Sissoo leaves
Objective: To evaluate the analgesic and antipyretic activities of alcoholic extract of Dalbergia sissoo leaves.
Methods: The peripheral analgesic activity of Dalbergia sissoo leaves (SLE; 100, 300 and 1000 mg/kg) was studied using acetic acid-induced writhing in mice and by Randall-Selitto assay. The central analgesic activity of SLE was studied using hot-plate method and tail-clip test in mice. The antipyretic activity of SLE was studied in Brewer’s yeast-induced pyrexia in rats.
Results: SLE significantly decreased the writhing movements in mice in acetic acid-induced writhing test. SLE (1000 mg/kg) significantly increased the pain threshold capacity in rats in Randall-Selitto assay and the reaction time in hot-plate test but not in tail-clip test. It also showed significant antipyretic activity in Brewer’s yeast-induced pyrexia in rats throughout the observation period of 6 h.
Dalbergiae Odoriferae Lignum extract
Dalbergiae Odoriferae Lignum is a traditional Chinese medicine (TCM) commonly used for promoting blood circulation, relieving pain and removing blood stasis. Volatile oil and flavonoid compounds are two main chemical constituents of Dalbergiae Odoriferae Lignum. Modern pharmacological studies show that Dalbergiae Odoriferae Lignum has many effects, such as relaxing blood, increasing blood flow of coronary, anti-oxidation, anti-inflammation and antitumor. Dalbergiae Odoriferae Lignum, as a characteristic TCM with the potential of further development, is generally compatible with other TCMs to treat cardio-cerebral vascular diseases. This article summarizes studies on chemical composition, pharmacological action, pharmacokinetic procfile in vivo and TCM compatibility in recent years, in order to provide references for further studies.
Daphne retusa
anti-inflammatory and analgesic effects of Daphne retusa Hemsl
Daphne retusa Hemsl. belongs to the genus Daphne, a member of Thymelaeaceae family. The barks and stems of Daphne retusa are used as a folkloric medicine ‘Zhu Shi Ma’ in Western China because of its effects of detumescence and acesodyne. In this paper, we investigate the anti-inflammatory and analgesic effects of the 75% ethanol extract of the stems and barks of Daphne retusa and different fractions partitioned with petroleum ether, methylene chloride, ethyl acetate and n-butanol, respectively.
The anti-inflammatory effects were evaluated using xylene-induced ear oedema in mice and carrageenan-induced paw oedema in rats, while the acetic acid-induced writhing test and hot-plate test as models for evaluating the centrally and peripherally analgesic activity. The results showed the plant has significant anti-inflammatory and analgesic effects (P < 0.05–0.01). Meanwhile, the result of the acute toxicity test at which the MTD was above 5 g/kg indicates that the plant extract is relatively safe in, and/or non-toxic to, mice. The findings of these experimental animal studies indicate that the Daphne retusa ethanol extract possesses anti-inflammatory and analgesic properties, and thus provide pharmacological support to folkloric, ethnomedical uses of ‘Zhu shima’ in the treatment and/of management of anti-inflammatory and painful conditions in China.
Desmodium triflorum (Linn.) DC. extract
analgesic and anti-inflammatory activities of Methanol extract from Desmodium triflorum DC in Mice
In this study, we evaluated the analgesic effect of methanol extract from Desmodium triflorum DC (MDT) by using animal models of acetic acid-induced writhing response and formalin test. The anti-inflammatory effect of MDT was investigated by λ-carrageenan-induced paw edema in mice. In order to study the anti-inflammatory mechanism of MDT, we detected the activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver, the levels of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic test, MDT (0.5 and 1.0 g/kg) decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. In the anti-inflammatory test, MDT (0.5 and 1.0 g/kg) decreased the paw edema at the 3rd, 4th, 5th and 6th hour after λ-carrageenan administration. On the other hand, MDT increased the activities of SOD and GRd in liver tissues and decreased the MDA level in the edema paw at the 3rd hour after λ-carrageenan-induced inflammation. MDT also affected the levels of interleukin-1β, tumor necrosis factor-α, NO and MDA which were induced by λ-carrageenan.
The results suggested that MDT possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MDT might be related to the decreases in the level of MDA in the edema paw via increasing the activities of SOD and GRd in the liver, and the NO level via regulating the IL-1β production and the level of TNF-α in the inflamed tissues.
Drymaria cordata Willd
analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd
Objectives: To study the analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd.
Materials and Methods: Wistar rats and Swiss albino mice were used for studying analgesic and anti-nociceptive activity of Drymaria cordata hydroethanolic extract (DCHE) at doses 50, 100 and 200 mg/kg p.o. Various models viz. acetic acid induced writhing model (female mice), Eddy’s hot plate (mice) and tail flick model (rat) for analgesic study and formalin-induced paw licking model (mice) were used for anti-nociceptive study.
Results: In acetic acid induced writhing model, effect of DCHE was better than the standard drug- indomethacin 10 mg/kg (p.o.). In the hot plate model, the maximum effect was observed at 60 min at a dose of 200 mg/kg p.o., which was higher than the standard drug morphine sulfate (1.5 mg/kg i.p.), whereas in the tail flick model, effect was comparable with morphine sulfate. In formalin-induced paw licking model, administration of DCHE completely abolished the early phase at 100 and 200 mg/kg p.o. and in the late phase, the effect of DCHE (200 mg/kg p.o.) was higher than indomethacin (10 mg/kg p.o.).
Conclusion: DCHE was effective in both non-narcotic and narcotic models of nociception, suggesting its possible action via peripheral and central mechanism. It also abolished the early phase in formalin-induced paw licking model, suggesting complete inactivation of C-fiber at higher dose. The activity can be attributed to the phyto-constituents viz tannins, diterpenes, triterpenes and steroids present in the DCHE extract. In conclusion, DCHE can be developed as a potent analgesic and anti-nociceptive agent in future.
Elettaria cardamonuum
Central and peripheral oxidative stress are important factors implicated in the pathogenesis of convulsions and pain respectively. antioxidant potential of Elettaria cardamomum (cardamom) seeds has been proven by several studies. phytochemical analysis of cardamom seeds have revealed the presence of phenolic compounds like flavonoids and tannins which are effective hydrogen donors capable of reducing oxidative stress. AIMS AND OBJECTIVES : To evaluate the anticonvulsant and analgesic properties of ethanolic extract of Elettaria cardamomum seeds in Wistar albino rats. MATERIALS AND METHODS : A total of 72 healthy Wistar albino rats (180-250 g) of either sex were included in the study and divided into 12 groups consisting of 6 animals each.
The ethanolic extract of Elettaria cardamomum seeds was prepared using cold maceration method and was tested at two graded doses (200 mg/kg BW and 400 mg/kg BW) given orally. Anticonvulsant property was evaluated using Maximal Electroshock [MES] model (standard – Phenytoin 10 mg/kg BW; i.p.) and Pentelenetetrazole [PTZ] model (standard – Sodium valproate 400 mg/kg BW i.p.). analgesic property was evaluated using tail warm water immersion method and writing test (standard – morphine 5 mg/kg BW i.p.). The results were expressed as Mean±SD. Statistical significance among study groups were carried out by using SPSS-16.0 version software, by applying One-way ANOVA followed by Dunnet’s post hoc test. results : The ethanolic extract of cardamom seeds showed significant (p<0.05) decrease in the mean scores of MES induced seizures at 400 mg/kg BW. 100% protection against Tonic Hind Limb Extension (THLE) was shown by both graded doses of the test drug. The onset of PTZ induced convulsions were delayed and the severity, number and scores of seizures were significantly reduced by cardamom extract at 400 mg/kg BW. At 400 mg/kg BW, there was a significant increase in the reaction time in tail warm water immersion test.
There was also significant reduction in total number of writhes and the and the percentage inhibition of writhes [90.28%] was comparable to the standard drugs. conclusion : The ethanolic extract of Elettaria cardamomum seeds possess significant anticonvulsant and analgesic properties in Wistar albino rats at the dose of 400 mg/kg BW.
epibatidine
Erythrina variegata Linn.peel extract
analgesic activity of Methanolic extract of the leaf of Erythrina variegata
Erythrina variegata (Synonym: Erythrina indica Lamk.; Bengali name- Mandar) is a medium sized deciduous small tree belonging to the family Papilionaceae. The plant grows all over the Bangladesh.1 The barks are used traditionally as astringent, febrifuge and in leprosy and fever. leaves are anthelmintic, laxative and diuretic. Paste of leaves is applied externally to cure inflammations and to relieve pain in the joints. Juice is also used to relieve earache and toothache.1 Previous phytochemical investigation showed that the stem bark contains three new isoflavones and a new isoflavanone.2 Seed contains a fixed oil, fatty acids and lectins.1 Though the plant is traditionally used in many parts of Bangladesh, no scientific report is available to validate the folkloric use.
As a part of our continuing studies on the medicinal plants of Bangladesh,3-5 the study was undertaken to evaluate the analgesic activity using acetic acid induced writhing and radiant heat tail-flick test in mice models. The leaf of the plant E. variegata was collected from Dhaka, Bangladesh in August 2004, and was identified by the experts at the Department of Botany, University of Dhaka. Collected plant parts, after cutting into small pieces, were dried and pulverized into a coarse powder, and stored into an air-tight container.
Eugenia supra-axillaris Spring. ex Mart leaf extract
Reactive oxygen species (ROS) are involved in the pathophysiology of several health disorders, among others inflammation. polyphenols may modulate ROS related disorders. In this work, thirty-two phenolic compounds were tentatively identified in a leaf extract from Eugenia supra-axillaris Spring. ex Mart. using HPLC-MS/MS, five of which were also individually isolated and identified. The extract displayed a substantial in vitro antioxidant potential and was capable of decreasing ROS production and hsp-16.2 expression under oxidative stress conditions in vivo in the Caenorhabditis elegans model. Also, the extract showed higher inhibitory selectivity towards COX-2 than COX-1 in vitro with higher selectivity towards COX-2 than that of diclofenac. The extract also exhibited anti-inflammatory properties: It attenuated the edema thickness in a dose dependent fashion in carrageenan-induced hind-paw odema in rats. In addition, the extract reduced the carrageenan-induced leukocyte migration into the peritoneal cavity at the highest dose.
Furthermore, the extract showed antipyretic and analgesic activities in a mouse model. Eugenia supra-axillaris appears to be a promising candidate in treating inflammation, pain and related oxidative stress diseases.
Evodia rutaecarpa (Juss.) Benth. fruit extract
The effects of 70% methanol extract (EA-ext) from Evodiae Fructus (EA) consisting of dried fruits of Evodia rutaecarpa var. bodinieri (Rutaceae) on nocicetive responses were investigated. oral administration of 50 or 200 mg.kg EA-ext had the same antinociceptive effect on writhing responses as induced by acetic acid. Its major alkaloidal constituents, evodiamine and rutaecarpine also had the antinociceptive effect. EA-ext significantly decreased the frequency of licking behavior within a unit of time at the late phase without affecting that of the early phase in the formalin test. EA-ext also increased nociceptive threshold of the inflamed paw without increasing that in the non-inflamed paw in the Randall-Selitto test. Although EA-ext inhibited the rise of vascular permeability induced by acetic acid and the increase of paw edema induced by carrageenin, it was ineffective on nociceptive response in the hot plate test and on locomotor activity.
These results suggest that EA possesses antinociceptive effects and its mode of action may be mediated by anti-inflammatory action, and that the antinociceptive constituents are only partially attributable to alkaloidal components mentioned above.
Ferula assa-foetida L.
antinociceptive effect of Ferula assa-foetida oleo-gum-resin in mice
Ferula assa-foetida L. is distributed throughout central Asia and Mediterranean area and grows wildly in Iran and Afghanistan. Asafoetida is an oleo-gum-resin that is the exudates of the roots of Ferula assa-foetida and some other Ferula species. In Iranian traditional medicine, asafoetida is considered to be sedative, analgesic, carminative, antispasmodic, diuretic, antihelmintic, emmenagogue and expectorant.
The aim of this study was to evaluate the antinociceptive effect of asafoetida in mice. The analgesic activity of asafoetida (25, 50 and 100 mg/kg) was compared with that of sodium diclofenac (30 mg/kg) or morphine sulfate (8 mg/kg) by using hot plate and acetic acid induced writhing tests. In hot plate test, the percentage of maximum possible effect (%MPE) against the thermal stimulus at 15 min post treatment time point for all doses of asafoetida was significantly greater than the control group. The number of writhes in all three doses of asafoetida was significantly less than the control group. GraphPad Prism 5 software was used to analyze the behavioral responses. Data were analyzed using repeated measure one-way ANOVA and P<0.05 was considered as the significant level. According to our findings, asafoetida exhibited a significant antinociceptive effect on chronic and acute pain in mice.
These effects probably involve central opioid pathways and peripheral anti-inflammatory action.
Ficus palmata L. fruit extract
Analgesic drugs like morphine and non-steroidal anti-inflammatory drugs exhibit several harmful effects. Here, we show for the first time the analgesic activity of Ficus palmata L. fruit extract (FPFE) on different analgesic rat models along with the in silico studies of some of the main phytochemicals of this plant. We performed in vivo pain models, along with in silico docking studies against the active site of COX-2 protein and mu-opioid receptors. A significant (p < 0.05) analgesic effect of FPFE was observed, and it was found that rutin has good pose and score as compared to diclofenac and morphinan antagonist (X-ligand), and psoralen has binding affinity almost equal to diclofenac, but a lower binding affinity as compared to rutin.
The results proved that F. palmata fruits have the potential to ameliorate painful conditions.
Flemingia strobilifera
Anil kumar et al., 2011 studied the potent analgesic activity of Flemingia strobilifera at the dose levels of 300, 500 and l000 mg/kg. The Flemingia strobilifera showed significant analgesic activity at low dose of 300 mg/kg even in the first hour of the test. The analgesic activity shown by Flemingia strobilifera at 300 mg/kg was almost comparable to that produced by acetylsalicylic acid, while at the dose levels of 500 mg/kg and 1000 mg/kg. Flemingia strobilifera showed better analgesic effect than the reference drug and at the dose level of l000 mg/kg the duration and intensity of analgesia was also greater than acetylsalicylic acid. The activity was also evaluated by Tail flick method (Chen et al.,1991).
Fragaria vesca
The aim of the study was to compare the analgesic activities of ethanolic extract of fruits and whole plant of Fragaria vesca in experimental animal models. The extracts were prepared by percolation method and oral toxicity testing was performed as per OECD guidelines. analgesic activity was assessed by tail flick method (for central action) and acetic acid-induced writhing test (for peripheral action). fruit extract, whole plant extract and aspirin showed significant analgesic activity, both central and peripheral, as compared to control (p<0.01).
Although fruit extract at dose of 500 mg/kg showed better activity than 250 mg/kg (p<0.05). analgesic activities of fruit extract 250 mg/kg and whole plant extract 500 mg/kg were almost equivalent while aspirin was most potent among all with significantly greater
Fumaria capreolata
anti-inflammatory and analgesic activities of ethanolic extract of Fumaria capreolata
Fumaria capreolata is used in traditional medicine for its gastrointestinal, hepatoprotective, and anti-inflammatory activities. The aim of the present study was to investigate the anti-inflammatory and the analgesic effects of the ethanolic extract of Fumaria capreolata (EFC) in mice. anti-inflammatory activity was evaluated by using the xylene-induced ear edema and multi-application of TPA induced chronic inflammation, whereas acetic acid-induced abdominal constrictions and formalin-induced licking and biting were used to determine antinociceptive effects. The crud extract of Fumaria capreolata (500 and 250 mg/kg) produced a significant inhibition of ear edema in two models of acute and chronic inflammation, and produced a significant reduction of the number of writhes. Also, in the formalin test, EFC reduced both neurogenic and inflammatory phases.
These findings suggest the aerial parts of Fumaria capreolata exhibits potent anti-inflammatory and analgesic activities on chemical behavioral models of nociception and inflammation in mice.
Gentiana kurroo Royle (Gentianaceae) root extract
The methanolic extract of roots of Gentiana kurroo Royle (Gentianaceae) an important and endemic medicinal plant of Kashmir Himalaya was screened for the presence of various bioactive plant metabolites and analgesic activity (using Eddy’s hot plate method and acetic acid-induced writhing test in Swiss albino mice at an oral dose of 250 and 500 mg/kg body weight). Diclofenac sodium (10 mg/kg b.w) was used as standard drug, whereas the vehicle (0.9% normal saline) was used as negative control. The phytochemical analysis revealed the Presence of tannins, alkaloids, saponins, cardiac glycosides, terpenes, flavonoids, phenolics, and carbohydrates. The extract showed stastically significant (P<0.05) analgesic activity in a dose-dependent manner, which were comparable with standard analgesic drug. In acetic acid-induced writhing test, the doses of 250 and 500 mg/kg b.w produced 63.38% and 73.70% inhibition of writhing reflex respectively as compared with the standard drug, which showed 71.61% inhibition. In eddy’s hot plate method the extract showed significant (P<0.05) increase in reaction time at different time of observation (0-120 min) in comparison with control.
The study clearly indicate that the crude methanolic root extract of Gentiana kurroo posses potent analgesic activity, which has provided some justification for the folkloric use of the plant as stomach-ache, pain, and anti-inflammatory.
Harpagophytum
Besides checking estimates of effectiveness and safety of using the proprietary Harpagophytum extract Doloteffin®, this postmarketing surveillance compared various disease-specific* and generic** measures of effect.
We enrolled 250 patients suffering from nonspecific low back pain (Back group: n = 104) or osteoarthritic pain in the knee (Knee group: n = 85) or hip (Hip group: n = 61). They took an 8-week course of Doloteffin® at a dose providing 60 mg harpagoside per day. The measures of effect on pain and disability included the percentage changes from baseline of established instruments (Arhus low back pain index*, WOMAC index*, German version of the HAQ**) and unvalidated measures (total pain index*, three score index*, the patient’s global assessment** of the effectiveness of treatment). Patients also received a diary for the daily recording of their pain and any additional treatments for it.
The three groups differed in age, weight and characteristics of initial pain. 227 patients completed the study. Multivariate analysis confirmed that several dimensions of effect were recorded by the several outcome measures but, in all groups, both the generic and disease-specific outcome measures improved by week 4 and further by 8. In multivariable analysis, the improvement tended to be more when the initial pain and disability score was more: older patients tended to improve less than younger, the hip group tended to improve convincingly more than the back group, whereas the improvement in the knee group was less readily differentiated from that in the back group. The subgroup of Back patients who required NSAIDs during the 8 weeks used significantly more per patient than patients in the other two groups, but that requirement also declined more with time. About 10% of the patients suffered from minor adverse events that could possibly have been attributable to Doloteffin®.
Between 50% and 70% of the patients benefitted from Doloteffin® with few adverse effects. Thus, Doloteffin® is well worth considering for osteoarthritic knee and hip pain and nonspecific low back pain.
Two daily doses of oral Harpagophytum extract WS 1531 (600 and 1200, respectively, containing 50 and 100 mg of the marker harpagoside) were compared with placebo over 4 weeks in a randomized, double-blind study in 197 patients with chronic susceptibility to back pain and current exacerbations that were producing pain worse than 5 on a 0–10 visual analogue scale. The principal outcome measure, based on pilot studies, was the number of patients who were pain free without the permitted rescue medication (tramadol) for 5 days out of the last week.
The treatment and placebo groups were well matched in physical characteristics, in the severity of pain, duration, nature and accompaniments of their pain, the Arhus low backpain index and in laboratory indices of organ system function. A total of 183 patients completed the study. The numbers of pain–free patients were three, six and 10 in the placebo group (P), the Harpagophytum 600 group (H600) and the Harpagophytum 1200 group (H1200)respectively (P=0.027, one-tailed Cochrane–Armitage test). The majority of responders’ were patients who had suffered less than 42 days of pain, and subgroup analyses suggested that the effect was confined to patients with more severe and radiating pain accompanied by neurological deficit. However, subsidiary analyses, concentrating on the current pain component of the Arhus index, painted a slightly different picture, with the benefits seeming, if anything,to be greatest in the H600 group and in patients without more severe pain, radiation or neurological deficit. Patients with more pain tended to use more tramadol, but even severe and unbearable pain would not guarantee that tramadol would be used at all, and certainly not to the maximum permitted dose.
There was no evidence for Harpagophytum-related side-effects, except possibly for mild and infrequent gastrointestinal symptoms.
Holarrhena antidysenterica leaves
A study on analgesic activity of Holarrhena antidysenterica leaves
The plant Holarrhena antidysenterica commonly known as ‘Kutaja’ belongs to the family Apocynaceae, is a small shrub or small tree evergreen in nature. The plant is medicinally important which is used to cure various diseases like diarrhea, dysentery, piles, biliousness and also with potent antioxidant activity. The analgesic activity of plant Holarrhena antidysenterica was evaluated by using the petroleum ether, chloroform and ethanolic extracts at the dose of 300, 300 and 250 mg/kg body weight respectively in the albino mice. The study was conducted as per the acetic acid induced writhing method. The ethanolic extract showed significant analgesic activity when compared to the standard Aspirin at the dose of 150 mg/kg of body weight.
The findings indicated that the ethanolic extract exhibited potent analgesic activity comparable to that of the standard drug
Hydrocotyle batrachium Hance
Background//Purpose: To investigate the analgesic and anti-inflammatory effects of a water extract of Hydrocotyle batrachium Hance (HBW) in mice.
Methoods: The analgesic effects of HBW were investigated by measuring the acetic acid-induced writhing response and the hind paw licking time following formalin injection. λ-Carrageenan (CARR)-induced paw edema was studied to explore the anti-inflammatory effect of HBW. The chromatograms of rutin, quercetin and HBW were obtained by high-performance liquid chromatography (HPLC).
Results: Treatment of male ICR mice with HBW (100, 500, 1000 mg/kg) inhibited the writhing response in a dose-dependent manner. The inhibitory effect of HBW at a dose of 1000 mg/kg was similar to that of indomethacin at a dose of 10 mg/kg. HBW significantly inhibited the degree of formalin-induced pain in the late phase. HBW (500, 1000 mg/kg) also inhibited the development of paw edema induced by CARR. The HPLC analysis revealed that rutin was an important bioactive compound in HBW.
Conclusion: HBW appears to have analgesic and ant-inflammatory activities.
Hydrocotyle umbellata L. (acariçoba) underground parts
The Hydrocotyle umbellata L. is a specimen of the Araliaceae family popularly known as acariçoba. Its indications in folk medicine include treatment of skin ulcers, and rheumatism. The aim of this study was to evaluate the antinociceptive and anti-inflammatory activities of the ethanolic extract from acariçoba’s underground parts (EEA). EEA reduced the nociceptive response of the animals as evaluated in the acetic acid-induced writhing test and in both phases of formalin test. EEA also presented a supraspinal analgesic activity by increasing the pain latency in the hot plate test.
Moreover, EEA reduced the leukocytes migration and plasma extravasation to pleural cavity in the carrageenan-induced pleurisy, besides reducing the edema induced by carrageenan until the second hour and also the edema induced by dextran. In conclusion our results showed that EEA of H. umbellata L. presents analgesic and anti-inflammatory activities, and that a blockade of activity or reduction in the release of different mediators, such as histamine and serotonin, could be involved in these pharmacologic effects.
hyperforin and hypericin
Ethnopharmacological relevance: Hypericum perforatum L. (Hypericaceae), popularly called St. John’s wort (SJW), has a rich historical background being one of the oldest used and most extensively investigated medicinal herbs. Many bioactivities and applications of SJW are listed in popular and in scientific literature, including antibacterial, antiviral, anti-inflammatory. In the last three decades many studies focused on the antidepressant activity of SJW extracts. However, several studies in recent years also described the antinociceptive and analgesic properties of SJW that validate the traditional uses of the plant in pain conditions.
Aim of the review: This review provides up-to-date information on the traditional uses, pre-clinical and clinical evidence on the pain relieving activity of SJW and its active ingredients, and focuses on the possible exploitation of this plant for the management of pain.
Materials and methods: Historical ethnobotanical publications from 1597 were reviewed for finding local and traditional uses. The relevant data on the preclinical and clinical effects of SJW were searched using various databases such as PubMed, Science Direct, Scopus, and Google Scholar. plant taxonomy was validated by the database plantlist.org.
Results: Preclinical animal studies demonstrated the ability of low doses of SJW dry extracts (0.3% hypericins; 3–5% hyperforins) to induce antinociception, to relieve from acute and chronic hyperalgesic states and to augment opioid analgesia. Clinical studies (homeopathic remedies, dry extracts) highlighted dental pain conditions as a promising SJW application. In vivo and in vitro studies showed that the main components responsible for the pain relieving activity are hyperforin and hypericin. SJW analgesia appears at low doses (5–100 mg/kg), minimizing the risk of herbal-drug interactions produced by hyperforin, a potent inducer of CYP enzymes.
Conclusion: Preclinical studies indicate a potential use of SJW in medical pain management. However, clinical research in this field is still scarce and the few studies available on chronic pain produced negative results. Prospective randomized controlled clinical trials performed at low doses are needed to validate its potential efficacy in humans.
Illicium verum Hook.f. fruit extract
The current investigation was designed to evaluate the analgesic, antipyretic, and anti-inflammatory effects of various extracts (methanol, ethanol, and aqueous) of dried fruit of Illicium verum hook.f, using 3 different doses (150, 250, and 350 mg/kg p.o) to verify the traditional uses of this spice. In the hot plate model of analgesia, ethanol extract showed a significant reduction in pain in a dose-dependent manner compared to the control group. The maximum effect was observed at 350 mg/kg dosage i.e., 16.90±0.17 s compared to the control group i.e., 5.03±0.05 s. The antipyretic activity was assessed in rats by Brewer’s yeast induction. The methanol and ethanol extracts produced a significant reduction in rectal temperature compared to the control group throughout the three doses.
The maximum effect was observed at 350 mg/kg dosage of ethanol extract i.e., 37.1±0.8* compared to the control i.e., 39.1±0.3. In the paw edema model, methanol and ethanol extracts disclosed a significant reduction in paw edema at 350 mg/kg of dose. The maximum effect was observed at 350 mg/kg dosage of ethanol extract i.e., 0.25±0.23* compared to the control i.e., 0.97±0.4. In a behavioral study, locomotor activity (rearing) and exploratory activity (grooming) in mice was reduced significantly at higher doses (350 mg/kg p.o) involving the three extracts.
However, scratching was increased non-significantly at all doses compared to the control group. This study concluded that various extracts of Illicium verum hook.f showed significant analgesic, antipyretic, and anti-inflammatory effects at different doses in a dose-dependent manner with varying potencies. The ethanol extract was found to be more potent among all, followed by methanol and aqueous extracts, whereas maximum effects were observed at 350 mg/kg of dose.
Impatiens balsamina
antinociceptive activity of methanol extract of flowers of Impatiens balsamina
Ethnopharmacological relevance: Impatiens balsamina Linn. (Balsaminaceae), an annual herb locally called “Dopati”, is cultivated as an ornamental garden plant in Bangladesh. flowers of the plant are used in folk medicine to treat lumbago, neuralgia, burns and scalds.
Aim of the study: This study evaluated the antinociceptive effect of the methanol extract of I. balsamina flowers (MIB).
Materials and methods: The extract was evaluated for antinociceptive activity using chemical- and heat-induced pain models such as acetic acid-induced writhing, hot plate, tail immersion and formalin test. To verify the possible involvement of opioid receptor in the central antinociceptive effect of MIB, naloxone was used to antagonize the effect. The effect of MIB on central nervous system (CNS) was also studied using hole cross and open field tests.
Results: MIB demonstrated strong and dose-dependent antinociceptive activity in all the chemical- and heat-induced mice models (p<0.05). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. The use of naloxone confirmed the association of opioid receptors in the central antinociceptive effect. MIB also showed significant central nervous system depressant effect (p<0.05).
Conclusion: This study reported the peripheral and central antinociceptive activity of the flowers of I. balsamina and rationalized the traditional use of the flower in the treatment of different painful conditions.
Imperata cylindrica Beauv. var. major (Nees)C.E.Hubb.root extract
Imperata cylindrica (L.) Beauv. (Poaceae family) is a perennial weed growing in tropical and subtropical areas and it is used in several herbal preparations to treat specific pathologic factors inducing pain. This work aimed to determine the in vitro antioxidant and in vivo anti-inflammatory, analgesic and antipyretic activities of the aerial parts of this plant. The methanol extract (MEIC) was used for (i) phytochemical fingerprint by High-Performance Liquid Chromatography (HPLC), (ii) total phenolic content (TPC) evaluation by the Folin-Ciocalteu colourimetric method, (iii) 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenger spectrophotometric assay, (iv) antioxidant capacity by Ferric reducing antioxidant Power (FRAP) assay, (v) analgesic activity evaluated with the acetic acid-induced writhing test, (vi) anti-inflammatory activity evaluation by carrageenan-induced paw oedema, (vii) antipyretic effect on lipopolysaccharide (LPS)-induced fever in rats, and (viii) acute and sub-chronic toxicity in mice.
The MEIC presented an average rate of TPC (1920.63 ± 360.62 mgGAE/100 g of dry weight (DW)), which is mostly represented by tannins (37.30%), organic acids (32.84%) and flavonols (10.88%). The DPPH free radical scavenger spectrometric assay showed the antioxidant capacity of the MEIC (IC50 = 192.07 ± 0.78 µg/mL) confirmed by the FRAP assay results (29.60 ± 0.55 mmol Fe2+/Kg of DW). The MEIC decreased significantly the number of writhing in a dose-dependent manner (p < 0.01) showing its analgesic activity; the extract inhibited the inflammation in a dose-dependent manner at the first stage (1st h, p < 0.01) and the second stage (3rd h, p < 0.001) post carrageenan induction and it demonstrated an antipyretic activity by lowering the body temperature (Tb) dose-dependently post LPS induction (i.p. route) and time-dependently at the dose of 200 mg/kg (p < 0.001) in mice. Moreover, the acute and sub-chronic toxicity in mice did not reveal any signs of toxicity and any changes in targeted biochemical and haematological parameters. The quantified phytocompounds could be at the origin of these pharmacological activities.
These findings support the beneficial use of this plant to alleviate pains and fever in inflammatory or other diseases. Further studies on the isolation of the bioactive compounds and their action mechanisms should be carried out to confirm these results.
analgesic and anti-inflammatory activities of Imperata cylindrica
The chloroform extract of the roots of Imperata cylindrica showed significant (p<0.001) antinocipetive activity in the acetic acid induce writhing model with 27.33 and 48.06% inhibition of writhing response at 150 and 300 mg/kg body weight. The analgesic activity in the radiant heat tail-flick model in mice also showed significant (p<0.01) increase in tail flick latency in a dose dependent manner (r=0.089). However, the anti-inflammatory activity in carrageenan induced rat paw inflammatory edema showed no significant reduction.
The analgesic effect of the Ethanol extract of the Cogon Grass Rhizome
(Imperata Cylindrica (L.) Beauv.) of Mice (Mus musculus)
Indonesia has known some traditional medicine. One of the plants used for traditional medicine is Imperata cylindrica (L.) Beauv. The new research has been found flavonoids in cogon grass rhizome. flavonoids might be to inhibitory action on cyclooxygenase synthesis. The aims of this research were to find out the existences of analgesic effect of cogon grass rhizome (Imperata cylindrica (L.) Beauv.) etha- nol extract on male mice. Laboratory experimental research with a complete randomized design were done with five groups and five replications to each group.
The treatment applied for those groups were: negative control (CMC 1% 0,2 ml/20 g BW), positive control (asetosal 5 mg/20 g BW), and goups A, B, and C respectively to get the ethanol extract of the cogon grass rhizome dose of 1 mg/ 20 g BW, 2 mg/ 20 g BW and 4 mg/20 g BW. The pain stimulus was given 15 minutes after treatment with the animal placed on a hotplate with temperature 550 C. Animals gave a response in the form licking legs. Interval between stimulus delivery and the occurrence of pain was called reaction time response. analgesic response was expressed positive if the reaction time after the test material was equal or greater than reaction time of positive control group or greater than three times the normal reaction time. The result of this research indicated that the ethanol extract of Imperata cylindrica (L.) Beauv. rhizome has analge- sic effect on male mice.
There were significant differences statistically between the groups extract 4 mg/ 20 g BW mice with the other treatment groups.
Jasminum amplexicaule
Jasminum amplexicaule Buch.-Ham. (Oleaceae) has been commonly used in the traditional medicine in dysentery, diarrhoea and bellyache in China. In the present work, the methanol extract of Jasminum amplexicaule and different fractions of this extract were studied for anti-diarrhoea and analgesic activities. The anti-diarrhoea activities were investigated using castor oil-induced, magnesium sulphate-induced diarrhoea models, antienteropooling assay and gastrointestinal motility models in mice. The analgesic activities were studied using hot-plate, writhing and formalin models in mice. At the doses of 100, 200 and 400 mg/kg, the methanol extract (ME) showed significant and dose-dependent anti-diarrhoea and analgesic activity in these models. The chloroform fraction (CHF), ethyl acetate fraction (EAF) and the residual methanol fraction (RMF) exhibited similar activity using a dose of 200 mg/kg in these models.
The pharmacological activities of the n-butanol fraction (BUF) were lesser than the ME extract and other fractions. These results may support the fact that this plant is traditionally used to cure diarrhoea and pain.
Juglans regia leaf extract
antinociceptive, anti-inflammatory and acute Toxicity effects of Juglans Regia L. leaves in Mice
Background: Juglans regia leaves have been used in folk medicine to alleviate inflammatory diseases. This study investigates the antinociceptive, anti-inflammatory and acute toxicity effects of Juglans regia L. leaves in mice.
Methods: 351 Male and female albino mice were divided into negative (saline), positive (morphine or diclofenac) controls as well as test groups (n=6-8). The acute (intraperitoneally) toxicity was evaluated for 2 days. antinociceptive activities were done using hot-plate and writhing tests. anti-inflammatory effects were studied using xylene induced ear edema and cotton pellet tests.
Results: The LD50 values of J. regia aqueous and ethanolic extrats were 5.5 and 3.3 g/kg, respectively. The aqueous (2.87 and 1.64 g/kg) and ethanolic (2.044 and 1.17 g/kg) extracts showed antinociceptive activity in hot-plate test. The pretreatment of naloxone (2 mg/kg, s.c.) did not inhibit the extracts activities. The extracts exhibited antinociceptive activity in writhing test, which were not blocked by naloxone. In xylene test, both extracts showed anti-inflammatory activity in some doses. The extracts showed anti-inflammatory activity against the chronic inflammation.
Conclusion: J. regia leaves demonstrated antinociceptive effect through non-opioid receptors and anti-inflammatory effect against acute and chronic inflammation. The extracts of J. regia could be considered as a promising analgesic and anti-inflammatory agents against diseases such as rheumatoid arthritis.
Kadsura interior A .C. Smith extract
Ethnopharmacological relevance: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by failure of spontaneous resolution of inflammation. The stem of Kadsura heteroclite (KHS) is a well-known anti-arthritic Tujia ethnomedicinal plant, which named Xuetong in folk, has long been used for the prevention and treatment of rheumatic and arthritic diseases.
Aim of the study: The analgesic and anti-inflammatory effects and the potential mechanisms behind such effects of KHS would be investigated by using different animal models.
Materials and methods: The abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid and the tail-flick response induced by radiant heat stimulation were used to evaluate the analgesic effect of KHS. The number of abdominal writhing episodes of mice and the latency of tail-flick in rats were measured and recorded. In acute inflammatory models, the ear edema of mice was induced by applying xylene on the ear surface, while the paw edema of male and female rats was induced by subcutaneous injection of carrageenan into the right hind paws of animals. The carrageenan-induced paw swelling in rats were selected as an anti-acute inflammatory mechanism of KHS. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) were measured by ELISA, and protein expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by Western blot.
Results: The maximal tolerated single dose of KHS was determined to be 26 g/kg in both sexes of mice. Pharmacological studies showed that KHS at the dose of 200 mg/kg significantly prolonged the reaction time of rats to radiant heat stimulation and suppressed abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid. KHS at the dose of 200, 400, and 800 mg/kg, showed dose-dependent inhibition of xylene-induced ear swelling in mice. KHS at the dose of 100, 200, 400, and 800 mg/kg demonstrated dose- and time-dependent suppression of paw edema induced by subcutaneous injection of carrageenan in both all rats. Mechanistic studies revealed that the anti-inflammatory effect of KHS was associated with inhibition of the production of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α and effectively decreased the expression of COX and iNOS proteins in the carrageenan-injected rat serum, paw tissues and inflammatory exudates. The positive reference drug, rotundine at a dosage of 100 mg/kg and indomethacin at a dosage of 10 mg/kg were used in both mice and rat models.
Conclusion: These results suggested that KHS has significant effects on analgesia and anti-inflammation with decreasing the pro-inflammation cytokines of IL-1β, IL-6, and TNF-α and inhibiting the proteins expression of COX-2 and iNOS.
Lactoferrin
Lactoferrin and Its potential Impact for the relief of pain: A Preclinical Approach
Pain is one of the most disabling symptoms of several clinical conditions. Neurobiologically, it is classified as nociceptive, inflammatory, neuropathic and dysfunctional. opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are conventionally prescribed for the treatment of pain. Long-term administration of opioids results in the loss of analgesic efficacy, leading to increased dosage, tolerance, and addiction as the main drawbacks of their use, while the adverse effects of NSAIDs include gastric ulcer formation, intestinal bleeding, acute kidney injury, and hepatotoxicity. Lactoferrin is an iron-binding, anti-inflammatory glycoprotein that displays analgesic activities associated, in part, by interacting with the low-density lipoprotein receptor-related protein (LRP), which may result in the regulation of the DAMP-TRAF6-NFκB, NO-cGMP-ATP K+-sensitive channel and opioid receptor signaling pathways.
This review summarizes and discusses for the first time the analgesic effects of lactoferrin and its presumable mechanisms based on pre-clinical trials. Given its anti-nociceptive and anti-inflammatory properties, lactoferrin may be used as an adjunct to enhance the efficacy and to decrease the tolerogenic effects of canonical therapeutic drugs prescribed for pain treatment.
Lactuca scariola
Seeds and samples of stems from the two medicinal plants, Lactuca scariola and Artemisia absinthium respectively were extracted in absolute methanol to determine their analgesic and anti-inflam- matory activity. The analgesic activity was assessed on intact mice by tail flick latency in tail immersion method. The anti-inflammatory activity was estimated volumetrically by measuring the mean increase in hind paw volume of rat with the help of plethysmometer. Acetylsalicylic acid in the dose of 300 mg/kg is used as standard drug. Both plant extracts were given in the doses of 300, 500 and 1000 mg/kg. Control group received 0.9% NaCI (saline) solution. All the doses administered orally. results showed that Lactuca had potent analgesic activity and Artemisia had significant analgesic and anti-inflammatory activity
Lamiophlomis rotata (Benth)Kudo extract
Ethnopharmacological relevance: Lamiophlomis rotata (Benth.) Kudo (L. rotata) is a medical plant that has been traditionally used for centuries for the treatment of pain, such as bone and muscle pain, joint pain and dysmenorrhea. Although iridoid glycosides of L. rotata (IGLR) are the major active components of it according to reports, it still remains poorly understood about the molecular mechanisms underlying analgesic effects of IGLR. The aim of the present study was to investigate the analgesic effect of IGLR on a spared nerve injury (SNI) model of neuropathic pain.
Materials and methods: The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. Then SNI rats were treated with IGLR for 14 days, using normal saline as the negative control. The paw withdrawal mechanical threshold (PMWT) in response to mechanical stimulation was measured by von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 9, 11, 13 and 14 after operation, respectively. After 14 days, the levels of nitric oxide (NO), nitric oxide synthase (NOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10) and cyclic guanosine monophosphate (cGMP) in the spinal dorsal horn were measured by the corresponding kits, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKGI) of spinal cord were analyzed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of N-methyl-D-aspartate receptor (NMDAR) and protein kinase C (PKCγ) of the spinal dorsal horn was performed by Western blot. Before all the experiments, motor coordination performance and locomotor activity had been tested.
Results: Our results showed that remarkable mechanical allodynia was observed on day 1 after operation in the SNI model, which was accompanied by a decrease in PMWT. treatment with IGLR (200, 400, 800 mg/kg) significantly alleviated SNI-induced mechanical allodynia, markedly decreased the levels of NO, NOS, TNF-α, IL-1β and cGMP, and increased the level of IL-10. Meanwhile, IGLR (200, 400, 800 mg/kg) also inhibited the protein expression of NMDAR, PKCγ and the mRNA expression of iNOS and PKGΙ in the spinal cord. In addition, gavage with the IGLR aqueous extract (800 mg/kg) did not signifiantly alter motor coordination or locomotor activity.
Conclusion: These results indicated IGLR could produce an anti-neuropathic pain effect that might partly be related to the inhibition of the NO/cGMP/PKG and NMDAR/PKC pathways and the level of TNF-α, IL-1β as well as to the increase of the level of IL-10 in spinal cord.
Lamiophlomis rotata (Benth.) Kudo is a perennial herb (Labiatae) used as the Tibetan traditional medicine with the effects of alleviating pain, detumescence, hemostasis, promoting blood circulation to remove blood stasis and reinforcing marrow. In this study, we investigated the antinociceptive and anti-inflammatory activities of iridoid glycosides extract of L. rotata (IGLR) in mice. Our results showed that the iridoid glycosides extract could decrease acetic-acid-induced writhings times and formalin-induced lickings times, inhibit carrageenan-induced hind paw edema and xylene-induced ear swelling, and suppress peritoneal capillary permeability and leukocyte infiltration also induced by acetic acid in mice.
All of these results suggested that the iridoid glycosides extract possesses the significant antinociceptive and anti-inflammatory activities.
Lamiophlomis rotata (L. rotata, Duyiwei) is an orally available Tibetan analgesic herb widely prescribed in China. Shanzhiside methylester (SM) is a principle effective iridoid glycoside of L. rotata and serves as a small molecule glucagon-like peptide-1 (GLP-1) receptor agonist. This study aims to evaluate the signal mechanisms underlying SM anti-allodynia, determine the ability of SM to induce anti-allodynic tolerance, and illustrate the interactions between SM and morphine, or SM and β-endorphin, in anti-allodynia and anti-allodynic tolerance. Intrathecal SM exerted dose-dependent and long-lasting (>4 h) anti-allodynic effects in spinal nerve injury–induced neuropathic rats, with a maximal inhibition of 49% and a projected ED50 of 40.4 μg. SM and the peptidic GLP-1 receptor agonist exenatide treatments over 7 days did not induce self-tolerance to anti-allodynia or cross-tolerance to morphine or β-endorphin.
In contrast, morphine and β-endorphin induced self-tolerance and cross-tolerance to SM and exenatide. In the spinal dorsal horn and primary microglia, SM significantly evoked β-endorphin expression, which was completely prevented by the microglial inhibitor minocycline and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. SM anti-allodynia was totally inhibited by the GLP-1 receptor antagonist exendin(9–39), minocycline, β-endorphin antiserum, μ-opioid receptor antagonist CTAP, and SB203580. SM and exenatide specifically activated spinal p38 MAPK phosphorylation.
These results indicate that SM reduces neuropathic pain by activating spinal GLP-1 receptors and subsequently stimulating microglial β-endorphin expression via the p38 MAPK signaling. Stimulation of the endogenous β-endorphin expression may be a novel and effective strategy for the discovery and development of analgesics for the long-term treatment of chronic pain.
Landolphia owariensis
anti-inflammatory AND analgesic activities OF leaf extracts OF LANDOLPHIA OWARIENSIS
The aqueous, methanol and chloroform extracts of Landolphia owariensis leaves (AELO, MELO & CELO respectively) wa investigated for anti-inflammatory and analgesic activities. All the extracts (100mg/kg each) were found to significantly (P<0.05 inhibit paw edema induced by carrageenan in rats and the nociception induced by Tail immersion in hot water (50.0 ± 1.0 0 C) and acetic acid. The methanol extract produced the highest paw edema inhibition while in thermally induced nociception both the MELO and CELO show high and comparable analgesic activity with acetylsalicylic acid (150mg/kg).
However in chemically induced pain (acetic acid) MELO produced the highest and comparable analgesic activity to acetylsalicylic acid (150mg/kg). We therefore conclude, that apart from the folklore uses of L. Owariensis leaves as antimalarial agents, the various extracts of the plant also possess anti-inflammatory and analgesic activities. phytochemical analysis showed that the methanollic extract of L. owerensis contain some secondary metabolites namely: alkaloids and some polyphenolic compounds. Also, this extract exhibits some anti-oxidative activities
Lecaniodiscus cupanioides root extract
analgesic activity of the aqueous root extract Lecaniodiscus cup anioides
Lecaniodiscus cupanioides is a medicinal plant that is widely used in folk medicine in West Africa. In Nigeria, the aqueous root extract of Lecaniodiscus cupanioides (LC) is reported to be effective against various ailments, including inflammatory conditions and hepatomegaly. Moreover, there are claims by herbal medical practitioners in Nigeria that LC is useful against acute and chronic pain, and that it is safe. This study reports the analgesic action of LC. The analgesic effect of LC (100 Š 400mg/kg, p.o.) was investigated in rodents using various pain models such as hot plate, formalin-induced pain, tail immersion, tail clip and writhing tests in mice, as well as tail flick test in rats.
The results showed that LC produced a significant (P<0.05) prolongation of the reaction times in the hot-plate, tail immersion, tail flick and tail clip tests and significantly and dose-dependently produced an increased pain threshold in both the first and second phases of the formalin pain test. In the writhing test, LC significantly inhibited writhing frequency. In all these models, with exception of tail clip and the first phase of formalin-induced pain tests, LC (400mg/kg) produced effects comparable (P<0.05, t-test) to the standard reference drugs, aspirin or morphine.
The results indicate that LC has a potent analgesic action, mediated centrally and peripherally, justifying its use in the management of pain in traditional African medicine.
Leonurus japonicus Sweet. extract
antioxidant effects and anti-aging characteristics of Leonurus japonicus H. ethanol extracts
Leonurus japonicus H. is a biennial wild plant that grows naturally in Asian countries such as Korea, China and Japan and belongs to Labiatae and has been used in lowering blood pressure, promoting urination, as a pain-killer, sedation and in promoting menstruation. In this study, Leonuri herba’s antioxidant function, improvement were investigated. L. japonicus H. extract was fractioned into Hexane, Ethyl Acetate, Water, H2O, 30% EtOH, 60% EtOH and 100% EtOH. The investigator carried out an experiment of confirming the capability of superoxide erasure by using the DPPH technique of antioxidant experiment and Xanthine oxidase hypoxanthine and measured the activation of antioxidant with ABTS technique. This Study showed that the 30% EtOH fraction was highest in antioxidant effect. Collagense synthesis was significantly increased in the experiment of anti-wrinkle effect. All the L. japonicus H. extracts inhibited the generation of H2O2 in a dose dependent manner.
Based on the above study findings, the anti-aging effect of 30% EtOH fraction of L. japonicus H. was most excellent. In conclusion, the rutin and adenosine of A.japonicus H. extract had a strong antioxidant function. If it is used in cosmetics, a variety of natural functional cosmetics, such as excellent natural moisturizers, antioxidant agents and anti-aging agent, can be developed.
Ethnopharmacological relevance: Leonurus japonicus Houtt. (Labiatae), commonly called Chinese motherwort (), is an herbaceous flowering plant native to Asia. For thousands of years in China, the aerial part of Leonurus japonicus has been used to treat menoxenia, dysmenorrhea, amenorrhea, lochia, edema of the body, oliguresis, sores, ulcerations and other diseases in women. Now, Leonurus japonicus is listed in the Pharmacopoeia of the People’s Republic of China. The present paper reviewed the ethnopharmacology, phytochemistry, biological actions and toxicology of Leonurus japonicus.
Materials and methods: Information on Leonurus japonicus was gathered via the Internet (using Elsevier, ACS, Medline Plus, CNKI, VIP, Web of Science, Google Scholar and Baidu Scholar) and libraries.
Results: Approximately 140 chemical compounds have been isolated from Leonurus japonicus, and the major components have been determined to be alkaloids, diterpenes and flavones. Among these active compounds, the effects of leonurine and stachydrine have been widely investigated. The primary active components in Leonurus japonicus possess wide pharmacological actions, such as effects on the uterus as well as cardioprotective, anti-oxidative, neuroprotective and anti-cancer activities.
Conclusion: Modern pharmacological studies have demonstrated that Leonurus japonicus has marked bioactivities, especially on the uterus and as a cardioprotective agent. These activities are related to its traditional use and provide prospects for the development of novel drugs, therapeutics and health care products for women. However, the toxicity of Leonurus japonicus will require further study, and the nomenclature for Leonurus japonicus will require additional clarification.
Leonurus japonicus Houtt. commonly called Chinese motherwort. The aerial parts was used to treat menoxenia, dysmenorrhea and some women`s diseases in China. Now, more than 130 chemical compounds have been isolated, and studies show that it possesses wide pharmacological actions
Ligularia fischeri
analgesic and anti-inflammatory effects of Ligularia fischeri leaves in experimental animals
Aim of the study: The ethanol extract (LF) of Ligularia fischeri var. spiciformis (leaf) has been evaluated for antinociceptive and anti-inflammatory activities in mice.
Materials and Methods: Analgesic and anti-inflammatory activities were studied by measuring nociception induced by formalin, acetic acid and hot-plate, and inflammation induced by carrageenan, formalin, and arachidonic acid.
Results: The acute treatment of mice with LF at doses of 100 and 200 mg/kg, by oral administration, produced a significant antinociceptive effect in the acetic acid-induced writhing, formalin-induced pain licking and hot-plate-induced pain. Also, the LF significantly inhibited both carrageenan- and formalin-induced inflammation as well as arachidonic acid-induced ear edema in mice.
Conclusion: These inhibitions were statistically significant (P < 0.05). Thus, our investigation suggests a potential benefit of Ligularia fischeri in treating conditions associated with inflammatory pain.
Ligusticum chuanxiong
effect and mechanism of senkyunolide I as an anti-migraine compound from Ligusticum chuanxiong
Results: Mice given senkyunolide I at 16 and 32 mg/kg had significantly elevated pain thresholds in the hot-plate test, and a dose of 32 mg/kg also reduced the number of abdominal writhing responses caused by acetic acid. significant improvements were observed in the neurotransmitter levels of the drug-treated rats compared with the saline-administered controls. Compared to the rats with nitroglycerin-induced migraines, the levels of nitric oxide in the plasma and whole brain of rats given senkyunolide I were lower.
Conclusion: The present study suggests that senkyunolide I may be an active component of L. chuanxiong, traditionally used to treat migraine. The mechanism of pain relief in migraine model rats may be through adjusting the levels of monoamine neurotransmitters and their turnover rates, as well as decreasing nitric oxide levels in the blood and brain. Therefore, senkyunolide I may be developed as a potential treatment for migraine pain.
Comparative analgesic effect of Ligusticum chuanxiong pieces and its products in mice
The present study was undertaken with the objective of finding out the comparative analgesic effect of Ligusticum chuanxiong (LC) pieces decoction, LC formula granule decoction, liquored LC pieces decoction and liquored LC formula granule decoction. The analgesic effects were analyzed using the hot plate and acetic-induced writhing test in mice, and antidysmenorrheic effect was observed with primary dysmenorrhea model. The results showed that four kinds of LC decoction had definite effect in delaying incubation period and decreasing the writhing frequency within 30 min. They also effectively relieved dysmenorrhea. Moreover, liquored LC had better analgesic effect than crude LC in four decoctions.
Ligusticum porteri
antinociceptive activity of Ligusticum porteri preparations and compounds
Context: The roots and rhizomes of Ligusticum porteri Coulter & Rose (Apiaceae) are widely used in Mexican folk medicine for several purposes, including painful complaints.
Objective: The main goal of this work was to demonstrate the analgesic action in mice of some preparations and major compounds from L. porteri.
Materials and methods: The extracts, aqueous (AE) and organic (OE), the essential oil (EO) and major compounds (10–316 mg/kg) from L. porteri were evaluated as potential antinociceptive agents using the acetic acid-induced writhing and hot plate tests in ICR mice.
Results: All preparations tested exhibited significant antinociceptive effect in the two animal pain models selected. AE and EO were more effective in the writhing test while OE had a better effect in the hot-plate model. On the other hand, Z-ligustilide (1) provoked an increment in the latency period to the thermal stimuli in the hot-plate test at a dose of 31.6 mg/kg, and a decrease in the number of abdominal writhes at 10 mg/kg. Z-3-butylidenephthalide (2) induced a dose-dependent antinociceptive action in the hot-plate assay; this compound was also effective for controlling the pain provoked by chemical irritation at the doses of 10 and 31.6 mg/kg. Finally, diligustilide (3) inhibited the number of writhing responses at all doses tested but was inactive in the hot-plate model.
Conclusion: The present investigation provides in vivo evidence supporting the use of L. porteri to treat painful conditions in folk medicine.
Litsea monopetala (LM) leaves extracts
Antioxidant, analgesic and antidiarrheal activities of Litsea monopetala (LM) leaves extracts were investigated in order to assessment of pharmacological activities. In vitro antioxidant properties, in vivo analgesic and antidiarrheal activities were investigated in this study. antioxidant plays a remarkable role to protect different kinds of diseases of human by inhibiting free radicals. 1, 1-diphenyl-2- picrylhydrazyl (DPPH) free radical scavenging was considered to evaluate the antioxidant property. analgesic and antidiarrheal activities were investigated in acetic acid induced writhing and castor oil induced antidiarrheal method by white albino mice, respectively. Methanolic extract of LM leaves has shown antioxidant activity with an IC50 value of 223.22 μg/ml which was compared to the standard ascorbic acid. This extract of LM at a dose of 500 mg/kg showed statistically significantly (p<0.001) and produced 68.75% writhing inhibition of mice while standard diclofenac sodium drug has shown 76.25% inhibition. LM also produced a significant (P<0.01) reduction in the frequency of diarrhea produced by castor oil in mice compared with Loperamide (50 mg/kg) standard.
This study clearly supports the medicinal value of LM`s leaves. However, further study is required to find out the active components which are responsible for these activities.
Mallotus repandus stem
The aim of our current study is to investigate the analgesic and anti-inflammatory potentials of methanolic extract of Mallotus repandus stem (MSM) using different in vivo assay models. analgesic and anti-inflammatory activities were evaluated using acetic acid induced writhing test, tail immersion method, hot-plate test, formalin induced hind paw licking, xylene induced ear edema, carrageenan-induced paw edema and cotton pellet induced granuloma in animal model at doses of 500, 1000 and 2000 mg/kg body weight. MSM showed significant (p < 0.05) analgesic activities in the acetic acid-induced writhing tests in mice. In the tail immersion and hot-plate test, MSM significantly prolonged the latency period (p < 0.05). significant (p < 0.05) formalin induced paw licking inhibition was observed at different doses and the highest 74.47% inhibition was observed at 2000 mg/kg.
Besides, MSM showed significant (p < 0.05) anti-inflammatory responses in carrageenan induced paw edema, xylene induced ear edema and cotton pellet induced granuloma methods. These findings suggest that the plant may be a potential source for the development of new analgesic and anti-inflammatory agent.
mangiferin
A Mangifera indica L. extract Could Be Used to treat neuropathic pain and Implication of Mangiferin
It has been accepted that neuroinflammation, oxidative stress and glial activation are involved in the central sensitization underlying neuropathic pain. Vimang is an aqueous extract of Mangifera indica L. traditionally used in Cuba for its analgesic, anti-inflammatory, antioxidant and immunomodulatory properties. Several formulations are available, and also for mangiferin, its major component. Preclinical studies demonstrated that these products prevented tumor necrosis factor α –induced IκB degradation and the binding of nuclear factor κB to DNA, which induces the transcription of genes implicated in the expression of some mediators and enzymes involved in inflammation, pain, oxidative stress and synaptic plasticity.
In this paper we propose its potential utility in the neuropathic pain treatment. This hypothesis is supported in the cumulus of preclinical and clinical evidence around the extract and mangiferin, its major component, and speculates about the possible mechanism of action according to recent advances in the physiopathology of neuropathic pain.
Menispermum dauricum Dc root extract
analgesic bisbenzylisoquinoline alkaloids from the rhizoma of Menispermum dauricum DC
Fifteen new bisbenzylisoquinoline alkaloids (1–15) were isolated from the rhizome of Menispermum dauricum DC. Compounds 1–9 were new N-oxides of dauricine-type alkaloids. Compounds 10–14 were rare tail-to-tail quaternary alkaloids. Their structures were characterized by comprehensive analysis of spectroscopic data, and absolute configurations were established from electronic circular dichroism (ECD) data and ECD calculations. Compounds were assayed on analgesic-related G-protein coupled receptors (GPCRs) including dopamine D1 and D2 receptors, opioid Mu receptor and muscarinic M3 receptor. Compound 1 showed high affinity and selective antagonistic activity on the M3 receptor with an IC50 value of 2.2 ± 0.5 μM; compound 15 exhibited the highest antagonistic affinity among the evaluated compounds on Mu (IC50 = 1.1 ± 0.6 μM) and it also acted as a D1 receptor antagonist (IC50 = 8.8 ± 2.9 μM).
These findings expanded the existing library of bisbenzylisoquinoline alkaloids and provided new structures for the related future drug design and synthesis.
Mentha spicata
Mentha spicata as natural analgesia for treatment of pain in osteoarthritis patients
Osteoarthritis, as the major cause of chronic musculoskeletal pain, impacts people aged 45 and above. The first line analgesic treatments have reported minimal short term effects. The use of essential oils as pain killer has increased, recently. Mentha spicata, or spearmint essential oil is famous due to its anti-flatulence effects, but one less known biological activity of spearmint is its analgesic activity. The aim of our study was to confirm the analgesic effects of M. spicata essential oil. In this review, we evaluated the articles on analgesic activities of M. spicata essential oil from different relevant databases (PubMed, Science Direct, Wiley, Taylor & Francis, and Springer) without limitation up to April 30, 2016.
Different animal studies have reported the analgesic effects of M. spicata essential oil and its main abundant compounds such as carvone, limonene and menthol, also, the efficacy and safety of spearmint oil in reducing of pain severity were confirmed in osteoarthritis patients. In spite of the beneficial effects of spearmint oil in reducing of pain, other large clinical trials are required to confirm the efficacy and safety of M. spicata oil.
Mimosa pudica
analgesic, antiepileptic, and behavioral study of Mimosa pudica (Linn.) on experimental rodents
Objective: Mimosa pudica (M. pudica) Linn. (family: Mimosaceae) is a traditionally used folk medicine to treat various ailments including convulsion, alopecia, diarrhea, dysentery, insomnia, tumor, wound, snake bite, etc., Here, the study was aimed to evaluate the potential on antiepileptic, analgesic, and motor activities of M. pudica leaves on rodents.
Materials and Methods: In an acute toxicity study, the extracts were administered in doses of 50-2,000 mg/kg/p.o. and behavioral changes were observed for up to 24 h. For a pharmacological study, the ethyl acetate extract of M. pudica (EAMP) leaves in doses of 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day were orally administered for consecutive 7 days to animals. The antiepileptic study was evaluated by inducing electric shock, pentylenetetrazole (PTZ), and isoniazid (INH) in mice, whereas the motor activity test was performed by using an actophotometer, rotarod test, and traction test in mice. The analgesic activity was done by hot-plate, tail flick, and acetic acid-induced writhing in rats. Statistical analysis was carried out by one-way analysis of variance (ANOVA) followed by Dunnett’s test.
Results: The EAMP showed dose-dependent analgesic activity by increasing the reaction time as compared to the vehicle control. Similarly, the motor performance was improved in dose-dependent manner as compared to standard. The doses (100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day) of the extract significantly (P < 0.01 and P < 0.001) reduced the duration of seizures induced by maximal electro shock (MES) and delayed the onset of tonic-clonic seizures produced by PTZ and INH. All the tested doses significantly prevented the latency and duration of convulsion against seizure inducers as compared to the vehicle controls.
Conclusion: These results revealed that the EAMP possesses potent analgesic, antiepileptic, and motor activities on animals. This could be an effective treatment option for various motor or seizure disorders.
antinociceptive activity Of Mimosa Pudica Linn
Mimosa pudica Linn (Mimisoideae) is a plant used in traditional medicine for various disorders. The aim of this work was to evaluate the acute toxicity and antinociceptive activity of the aqueous extract of Mimosa pudica in animal models. In the acute toxicity study, a single dose of aqueous extract of 2000 mg kg-1 body weight p.o. was administered. For 48 h, animals showed no clinical signs and mortality. In the acetic acid-induced writhing model, the extract at a dose of 200 & 400 mg kg-1 body weight showed significant (p<0.001) inhibition of writhing response of 46.24 and 56.0% respectively. In the hot plate test, the extract produced a significant (p<0.001) increase in the latency in a dose-related manner. This study established the analgesic properties of Mimosa pudica Linn.
EVALUATION OF analgesic AND anti-inflammatory potential OF MIMOSA PUDICA LINN
The aim of this work to evaluate the acute toxicity, analgesic and anti-inflammatory activity of Ethanolic extract of Mimosa Pudica Linn. In the acute toxicity study, the extracts were administered in doses of 5, 50, 300 and 2000 mg/kg p.o. and behavioral changes were observed after 24 hrs. In hot plate test the pethidine treated group, Tail flick Diclofenace treated group, and group given ethanolic extracts as 250 mg/kg and 500 mg/kg showed increase in latency time dose dependent manner. oral administration of ethanolic extract at a dose of 500 mg/kg showed significantly reduction of writhing response induced by acetic acid as compared the dose given at 250 mg/kg.
mitragynine
Pain remains a very pervasive problem throughout medicine. Classical pain management is achieved through the use of opiates belonging to the mu opioid receptor (MOR) class, which have significant side effects that hinder their utility. Pharmacologists have been trying to develop opioids devoid of side effects since the isolation of morphine from papaver somniferum, more commonly known as opium by Sertürner in 1804. The natural products salvinorin A, mitragynine, and collybolide represent three nonmorphinan natural product-based targets, which are potent selective agonists of opioid receptors, and emerging next-generation analgesics. In this work, we review the phytochemistry and medicinal chemistry efforts on these templates and their effects on affinity, selectivity, analgesic actions, and a myriad of other opioid–receptor-related behavioral effects.
Morinda Citrifolia
analgesic and antiinflammatory activity of Morinda citrifolia L. (Noni) fruit
M. citrifolia is a tropical plant with a long tradition of medicinal use in Polynesia and tropical parts of eastern Asia and Australia. One of its favorite uses is the treatment of painful inflammatory conditions, such as arthritis. The analgesic activity of Noni fruit puree on mice was investigated using the hot plate test. A 10% solution of freeze concentrated Noni fruit puree in the drinking water of mice reduced the pain sensitivity comparably to the central analgesic drug tramadol. This effect was only partly reversed by the application of the morphine antagonist naloxone. An alcohol extract of noni fruit puree also caused an inhibition of MMP-9 release from human monocytes after stimulation with LPS. This effect was comparable to hydrocortisone (10−5 m). The findings suggest that preparations of noni fruits are effective in decreasing pain and joint destruction caused by arthritis.
analgesic effect OF THE ALCOHOLIC extract FROM THE fruits OF MORINDA CITRIFOLIA
The alcoholic extract from the fruits of Morinda citrifolia (noni) was evaluated for analgesic effect in mice using the acetic acid-induced writhing test. The extract was administered by i.p. injection in doses of 1, 2, 3 and 4 g of dried plant material kg-1 of animal body weight, 15 min before i.p. injection of acetic acid (0.75%). morphine sulfate (1.5 mg kg-1, i.p.) was used as the reference drug. Control animals received i.p. injections of 0.9% NaCl solution, instead of the extract. In control mice, the number of writhes during the 20 min test period was 43.0 ± 1.4 (mean ± S.E.M., n=6). The extracts produced a significant dose-dependent inhibition of acetic acid-induced abdominal constriction. The percentage inhibition was 4.4 ± 4.5, 21.2 ± 11.2, 71.4 ± 5.0, 93.1 ± 1.7 (mean ± S.E.M., n=6) at the doses of 1, 2, 3 and 4 g kg-1 respectively, compared to control animals. The inhibitory effect of the 4 g kg-1 dose of extract was similar to that produced by morphine in a dose of 1.5 mg kg-1. The antinoniceptive effect in writhing test was statistically significant (p<0.001) for 15 min until 5 hr of administration. The data obtained suggest that the alcoholic extraction from the fruits of Morinda citrifolia appears to have analgesic effect. Further studies are necessary for the identification of the active principles and more detailed elucidation of its mechanism of action is required.
antinociceptive activity of freeze dried powdered Morinda citrifolia L. fruit
Objective: The main objective of the study was to establish the antinociceptive action of freeze dried powdered Noni against Swiss albino mice with the help of various in vivo analgesic models.
Method: Antinociceptive effect of powdered freeze Dried Noni at doses 250 and 500mg/kg b.w was established in Swiss albino mice through acetic acid induced writhing test, radiant heat model, tail immersion model and formalin induced pain model. Diclofenac (10mg/kg) and Pethidine (10mg/kg) were taken as reference for peripheral and central action. Naloxone (2mg/kg) was used to confirm the central action of Noni.
Result: It was found that the oral administration of Noni causes significant (p<0.01) reduction in writhes with Diclofenac as standard. significant (p<0.01) and dose dependent increase in the reaction time in radiant heat and tail immersion model revealed the central antinociceptive effect of Noni. In Formalin induced pain model, Noni (500mg/kg) showed significant inhibition of paw biting and licking events in both the phases of pain. Inhibition of analgesic activity on i.p administration of Naloxone in tail flick test of Noni and Pethidine confirmed the central action of Noni.
Conclusion: Thus it was revealed that Noni has significant analgesic activity and act through both mechanisms central as well as peripheral.
Moringa oleifera Lam extract
analgesic activity of seeds of Moringa oleifera Lam
Moringa oleifera Lam. Seed has been documented to posses antimicrobial and water purifying activities and also used in the treatment of gout, eye infections and in arthritis. Th e alcoholic extract of leaves of Moringa oleifera Lam. were reported to have analgesic activity but seed still not reported. Th e eff ect of alcoholic extract and its various fractions as Petroleum ether, Ethyl acetate, Diethyl ether, n-Butanol were tested for qualitative analysis which contain glycosides, flavonoids, tannins, amino acids (alpha-4rhamnoloxy benzyl isothiocynate). Th e extracts were also tested for their analgesic activity was carried out by using Hotplate and Tail immersion method.Aspirin (25 mg/kg) was used as a standard.
analgesic effect of ethanolic leaf extract of moringa oleifera on albino mice
Objectives: Moringa oleifera is a highly valued plant distributed in many countries of the tropic and subtropics. Moringa oleifera leaves are a potential source of phytochemical ingredients claimed to have analgesic property. pain is an unpleasant sensation, which in many cases represents the only symptom for the diagnosis of several diseases. Therefore analgesic drugs lacking the side effect as alternative to nonsteroidal anti-inflammatory drugs (NSAIDs) and opiates are in demand by the society. The present study is undertaken to evaluate the analgesic activity of Moringa oleifera using acetic acid induced writhing test and Eddy’s hot plate test.
Materials and Methods: It is a randomized control study. The present study was done using two experimental models. The albino mice were divided into six groups, each group consisting of 6 mice. A total of 36 mice were used in each of the two experimental models. Group I: Control (normal saline given orally at 2 ml/kg body weight); Group II: Standard (diclofenac 10 mg/kg i.p/ morphine 1 mg/kg i.p); Group III, IV, V, VI (ethanolic extract of Moringa oleifera (EMO) 50, 100, 200, 400 mg/kg, respectively). The EMO leaves were administered at 50, 100, 200, 400 mg/kg doses orally 1 hour before the experiments. For peripheral analgesic effect, acetic acid induced writhing test was used. The central analgesic effect was screened using Eddy’s hot plate method. The standard drug used in acetic acid induced writhing test was diclofenac and in Eddy’s hot plate test was morphine.
Results: The EMO leaf showed significant (P < 0.01) analgesic activity at 100, 200, 400 mg/kg in the acetic acid induced writhing test showing 32.21%, 59.71% and 78.61% inhibition of writhes, respectively in comparison with the control. In the Eddy’s hot plate test EMO at 400 mg/kg showed significant (P < 0.01) analgesic activity from 15 min to 90 min with a mean rank ranging from 28.92 to 26.00, second mean rank following morphine in comparison with control. In both the tests, EMO showed significant (P < 0.01) analgesic activity in a dose-dependent manner.
Conclusion: The ethanolic leaf extract of Moringa oleifera exhibited analgesic activity in both models showing its both central and peripheral analgesic actions.
Moringa oleifera, a species with potential analgesic and anti-inflammatory activities
Moringa oleifera has long been used in large demand in folk medicine to treat pain. The present study was undertaken to examine the antinociceptive and anti-inflammatory spectrum of M. oleifera leaf extracts discriminating the constituents’ nature by using different kind of experimental models in rats. Pharmacological evaluation of a non-polar and/or polar extracts at several doses (30–300 mg/kg, p.o.) was explored through experimental nociception using formalin test, carrageenan-induced paw edema and arthritis with subcutaneous injection of collagen in rats. Basic morphology characterization was done by scanning electronic microscopy and laser scanning confocal microscopy. Not only polar (from 30 or 100 mg/kg, p.o.) but also non-polar extract produced significant inhibition of the nociceptive behavior with major efficacy in the inflammatory response in different assessed experimental models. This antinociceptive activity involved constituents of different nature and depended on the intensity of the induced painful stimulus. phytochemical analysis showed the presence of kaempferol-3-glucoside in the polar extract and fatty acids like chlorogenic acid, among others, in the non-polar extract.
Data obtained with M. oleifera leaf extracts give evidence of its potential for pain treatment.
Objective: Moringa oleifera (family Moringaceae) has been widely used in African folk medicine, and researchers have recently revealed its anti-inflammatory effects in human. This study aimed to evaluate the analgesic properties of methanolic extracts of M. oleifera in complete Freund’s adjuvant (CFA)-induced arthritis in rats.
Methods: Adult male Wistar rats, weighing 200 to 220 g, were used in this study. Adjuvant arthritis was induced on day 0 by a single subcutaneous injection of CFA. The prepared extracts from both the root and leaf (200, 300 and 400 mg/kg) of M. oleifera were administered intraperitonealy to rats in the treatment groups 0, 3 and 6 d after CFA injection and indomethacin (5 mg/kg) was used as a positive control drug. Thermal hyperalgesia and mechanical allodynia were evaluated for the analgesic effect 0, 3 and 6 d after CFA injection. Combined methanolic root and leaf extracts of M. oleifera (200 mg/kg) were also tested for the analgesic effect.
Results: The potency of the root or leaf extracts of M. oleifera (300 and 400 mg/kg) was similar to that of indomethacin, resulted in significant reductions in both thermal hyperalgesia and mechanical allodynia in rats with CFA-induced arthritis compared with the control group after 3 and 6 d, respectively (P<0.01 or P<0.05). Combined root and leaf extracts (200 mg/kg) of M. oleifera resulted in a significant reduction in thermal hyperalgesia compared with the control group after 3 and 6 d, respectively (P<0.01). Prophylactic injections of combined root and leaf extracts of M. oleifera (200 mg/kg) resulted in a significant reduction in thermal hyperalgesia compared with the control group, the root extracts group, and the leaf extracts group after 3 and 6 d, respectively (P<0.01).
Conclusion: The methanolic extracts of the root or leaf of M. oleifera are effective in the reduction of pain induced by CFA in rats. A comparison of single and combination therapies of root and leaf extracts also showed a synergistic effect on pain reduction.
anti-inflammatory and analgesic activity of stem bark of Moringa Oleifera.
The present study evaluates the anti-inflammatory and analgesic activities of various extracts of stem bark of Moringa oleifera using various experimental models. The analgesic activity of stem bark of Moringa oleifera carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. The effects of the administration of reference standard (diclofenac) were also evaluated. Two different extracts (Petroleum ether and Methanolic) of Moringa oleifera at the dose level of 100,200 and 400 mg/kg, p.o. were tested. treatment with Methanol extract (100, 200, and 400 mg/kg, p.o.) showed significant (p<0.01) inhibition of carrageenan induced rat paw edema. maximum inhibition was observed at 400 mg/kg dose as compared to the control , cotton pellet granuloma formation and acetic acid-induced writhing; however, pet ether and methanolic extracts (400 mg/kg, p.o.) were found to be more effective in increasing latency period in tail flick method.
The results obtained indicate that Moringa oleifera has analgesic and antiinflammatory activities that supports the folk medicinal use of the plant.
Nardostachys chinensis Batal.root extract
Four novel guaianoids, nardoguaianone A, B, C and D, were isolated from Nardostachys chinensis roots. The structures were elucidated by spectral means and chemical transformation. antinociceptive activities of the constituents of N. chinensis, including some of the above novel compounds, were investigated by the formalin test. As a result, it was revealed that nardoguaianone A and D showed activity at the second phase of pain induced by formalin injection.
Nigella sativa seeds
analgesic effect of Nigella sativa seeds extract on Experimentally induced pain in Albino Mice
Objective: To determine the analgesic effect of ethanolic extract of Nigella sativa seeds on experimentally-induced pain in albino mice.
Study Design: Randomized controlled trial (RCT). Place and Duration of Study: Physiology Department, Services Institute of medical Sciences (SIMS), Lahore, from May to September, 2009.
Methodology: The study was carried out in 90 male albino mice using acetic acid induced writhing test as a chemical model of nociception. The mice were divided in three groups of 30 each. Group A was given normal saline (control); group B was given Nigella sativa seed extract in a dose of 50 mg/kg; and group C received diclofenac sodium, as a reference drug. Number of writhings in treated and control groups were compared.
Results: The ethanolic extract of Nigella sativa seeds given intraperitoneally caused significant (p < 0.05) analgesic effect on nociceptive response initiated by 0.6% acetic acid; although this analgesic effect was less than that produced by diclofenac sodium.
Conclusion: Ethanolic extract of Nigella sativa possessed significant analgesic effect in mice.
Nyctanthes arbor-tristis Linn. stem bark extract
Stem bark of Nyctanthes arbor-tristis Linn. was extracted in methanol to evaluate their analgesic and anti-inflammatory activities. The analgesic activity was determined on Wistar albino rats by hot plate method, tail flick assay, and tail immersion method using morphine sulphate as standard drug at a dose of 5 mg/kg of body weight and the results were expressed as mean increase in latency after drug administration ± SEM. The anti-inflammatory activity was assessed by Carrageenan-induced rat paw oedema using diclofenac sodium as standard drug at a dose of 100 mg/kg of body weight and expressed in terms of mean increase in paw volume ± SEM. stem bark extract was given at a dose of 250 mg/kg and 500 mg/kg of body weight. Both standard drugs and extract were administered orally to the animals. Control received distilled water orally. results showed that Nyctanthes arbor-tristis Linn. had potent analgesic and anti-inflammatory activities.
Ocimum basilicum L extract
STUDY THE analgesic AND sedative effect OF Ocimum basilicum ALCOHOLIC extract IN MALE RATS
This study was carried out on male rats to evaluate the analgesic and sedative effect of different doses of Alcoholic extract of Ocimum basilicum leaves. The analgesic effect studied by using formalin test, 20 male rats divided to a four groups (5 each), first group exposed water orally only before injection of formalin, second group exposed orally with Diclofenac at a dose 0.71mg/kg B.W before injection of formalin, Third and fourth groups orally incubated with Alcoholic extract of Ocimum basilicum leaves at a dose (50 and 100mg/kg BW) respectively. While the sedative effect studied by using pentobarbitone sleeping time test and open field test, in each test 15 male rats used and divided to a three groups one of them treated with distillated water and the other two groups treated with Alcoholic extract of Ocimum basilicum leaves at a dose (50 and 100mg/kg BW) respectively. results of formalin test showed a significant reduction in the mean value of nociceptive response in Diclofenac group specially at late phase while, groups treated with Alcoholic extract of Ocimum basilicum leaves revealed a significant reduction in the nociceptive response value at the both phases (early and late phase) moreover the group treated with 100mg/kg showed the highest attenuation in the mean value of nociceptive response compared to 50mg/ kg treated group.
Furthermore, the dose 100mg/kg produced the potent sedative effect in pentobarbitone sleeping time test and open field test. These results pointed to analgesic and sedative effect of Ocimum basilicum may duo to its consistence of the active analgesic and sedative compounds and its effect are in a dose dependent manner
antinociceptive effect of Volatile Oils from Ocimum basilicum flowers on Adult Zebrafish
The species Ocimum basilicum L., Lamiaceae, is popular for culinary purposes and medicinal use as a larvicide, repellent, antifungal, and antimicrobial agent. Therefore, the aim of the present study is to evaluate the chemical composition and antinociceptive effect of the volatile oil of O. basilicum flowers using adult zebrafish (Danio rerio) (n = 6/group) treated orally (20 µl) with volatile oil (0.25, 1.25, or 2.5 mg/ml; 20 µl) or vehicle (0.9% NaCl, 20 µl). The volatile oil of the O. basilicum flowers was obtained by hydrodistillation and analyzed by GC–MS, and the antinociceptive action is evaluated by different stimuli using motor parameters. The analysis of the chemical profile identified fourteen components with linalool (1) as a major chemical constituent (56.37%). The oral administration of volatile oil did not show any acute toxicity or behavior effects in all tested doses. The volatile oil has a pharmacological potential for the treatment of acute pain by modulation of opioid system, N-methyl-d-aspartate receptors (glutamatergic receptor), and the transient receptor potential vanilloid subtype 1 and acid-sensing ion channels.
Together, these data provide support for analgesic properties of the volatile oil and contribute to suggest that the adult zebrafish model presents the cheapest, cost-effective pharmacological alternative for the discovery of novel analgesics.
Onosma bracteatum
Onosma bracteatum wall: A potent analgesic agent
Background: This study was aimed to find out the central and peripheral analgesic activity of hydro methanolic extract of aerial parts of Onosma bracteatum.
Material and methods: The central and peripheral analgesic activity is evaluated by tail flick test and acetic acid induced writhing test at the doses of 50, 100, 250 and 500mg/kg body weight respectively in animal models.
Results: The results obtained from Tail flick test revealed that O. bracteatum possesses potent analgesic effects by inducing significant increase in latency period in dose dependent manner at all doses at 1, 2 and 3 hours post feeding respectively. The maximum effect was observed at a dose of 500mg/kg i.e. 258.9% (p<0.05) at 3hrs post feeding. Diclofenac sodium (5mg/kg body weight) run as standard also increased the latency period continuously and highest activity was noted at 3hr i.e. 284.5% (p<0.05). Acetic acid induced writhing test also showed significant activity in a similar manner by O. bracteatum i.e 54% (p<0.05) at 500mg/kg while standard drug Diclofenic sodium (5mg/kg body weight) showed 45.9% (p<0.05) activity.
Conclusion: It is concluded that O. bracteatum possesses significant central and peripheral analgesic activity in animal model.
Opuntia dillenii (Ker Gawl.) Haw. extract
Opuntia dillenii (Ker-Gawl) Haw is a cactus that belongs to the family Opuntiae. Lyophilized aqueous extract of the fruits of the plant, used in Canarian traditional medicine for gastrointestinal and bronchial troubles, was evaluated for analgesic and anti-inflammatory properties in rats and mice. The Opuntia dillenii extract (100–400 mg/kg, i.p.) inhibited, in a dose-related manner, carrageenan-induced paw edema in rats. A dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, with doses of 50 and 100 mg/kg.
Opuntia dillenii (Nagphana) traditionally used against inflammation and also possess analgesic effect. Thus in the present study analgesic properties of O. dillenii cladode methanol extract, its fractions obtained via vacuum liquid chromatography along with isolated α-pyrones, opuntiol and its glucoside, opuntioside were analyzed. The acetic acid-induced writhes were reduced by O. dillenii test agents with opuntioside being most effective (IC<sub>50</sub> 26 ± 0.9 mg/kg) and equipotent to diclofenac and β-sitosterol. Consistently, it also elicited most potent effect (IC<sub>50</sub>: 28 ± 1.1 and 24 ± 1.2 mg/kg) during early and late phases of formalin-induced paw licking, producing effect similar to diclofenac and indomethacin. It was also most effective in hot plate test. Naloxone (opioid antagonist) reversed the analgesic effects of extract and fractions but failed to antagonize the opuntiol and opuntioside analgesic effects.
In conclusion, edible O. dillenii extract, its fractions, opuntiol and opuntioside reduced peripheral and centrally mediated pain via opioid dependent and independent systems. Among them opuntioside emerged as most effective analgesic possibly due to the presence of glucose moiety at position 7 of its α-pyrone ring. This is the first report of opuntiol and opuntioside analgesic effect which may serve as lead compounds in designing of new analgesics.
analgesic and anti-inflammatory action of Opuntia elatior Mill fruits
Background: Opuntia elatio Mill is a xerophytic plant with potentially active nutrients. It is traditionally appreciated for its pharmacological properties; however, the scientific information on this plant is insufficient.
Objective: The present study evaluates the antinociceptive and anti-inflammatory action of prickly pear.
Materials and Methods: Writhing and tail-immersion tests were carried out to evaluate analgesic action, while the carrageenan-induced paw edema and neutrophil adhesion tests were conducted in Albino wistar rats to assess anti-inflammatory action.
Results: ED50 values of the fruit juice in writhing, tail immersion, and paw edema test were 0.919, 2.77, and 9.282 ml/kg, respectively. The fruits of Opuntia produced analgesic and anti-inflammatory action in a dose-dependent manner.
Conclusion: The results establish the folklore use of prickly pear may be due to the presence of betacyanin and/or other phenolic compounds.
Oroxylum indicum (L.) Vent. seed extract
phytochemical Screening and Evaluation of analgesic activity of Oroxylum indicum
We aimed to study phytochemical screening and analgesic activity of ethanol extract of Oroxylum indicum. The dried powder of the barks of the plant was extracted with 95% ethanol and was subjected to various phytochemical tests to ascertain the principle constituents contained in the extract.
The result revealed the presence of alkaloids, flavonoids, tannins, glycosides in the ethanol extract of Oroxylum indicum. The extract was screened for analgesic activity by using hot plate, acetic acid-induced writhing and formalin test. The ethanol extract of the plant at two different doses (250 and 500 mg/kg) showed significant (P<0.05) analgesic effect in all test methods (hot plate, acetic acid-induced writhing and formalin). The analgesic activity was compared with a standard drug (ketorolac at 10 mg/kg). Based on the present findings and previous literature review it can be concluded that flavonoids and tannins might be responsible for the analgesic activity. We suggest that ethanol extract of Oroxylum indicum might have potential chemical constituents that could be used in the future for the development of novel analgesic agent.
inflammation is all a pervasive phenomenon, which is elicited by the body in response to obnoxious stimuli as a protective measure. However, sustained inflammation leads to several diseases including cancer. Therefore it is necessary to neutralize inflammation. Sonapatha (Oroxylum indicum), a medicinal plant, is traditionally used as a medicine in Ayurveda and other folk systems of medicine. It is commonly used to treat inflammatory diseases including rheumatoid arthritis and asthma. Despite this fact its anti-inflammatory and analgesic effects are not evaluated scientifically. Therefore, the anti-inflammatory and analgesic activities of Sonapatha (Oroxylum indicum) were studied in Swiss albino mice by different methods. The hot plate, acetic acid, and tail immersion tests were used to evaluate the analgesic activity whereas xylene-induced ear edema and formalin induced paw edema tests were used to study the anti-inflammatory activity of Sonapatha.
The administration of mice with 250 and 300 mg/kg b.wt. of O. indicum reduced pain and inflammation indicating that Sonapatha possesses analgesic and anti-inflammatory activities. The maximum analgesic and anti-inflammatory activities were observed in mice receiving 300 mg/kg b.wt. of O. indicum ethanol extract. Our study indicates that O. indicum possesses both anti-inflammatory and analgesic activities and it may be useful as an anti-inflammatory agent in the inflammation related disorders.
The aim of this study is to examine possible antioxidant, analgesic and anti-inflammatory activities of the stem bark of Oroxylum indicum, an endemic plant of Northeast India. The hydro-alcoholic extract was evaluated for their antioxidant activity by using DPPH scavenging method and phenolic and flavanoid content was estimated. The analgesic and anti-inflammatory assays were carried out on adult male Wistar albino rats by hot plate and carrageenan-induced paw edema method. The content of phenolic and flavanoid compound in hydroalcoholic extract in terms of gallic acid and quercetin equivalent (GAE) is 52.67 mg/L and 64.63 mg/L respectively. The extract showed antioxidant activity with IC50 value of 39.82 -g/mL as compared to the ascorbic acid which exhibited IC50 value of 26.17 -g/mL. The analgesic activity was assayed by hot plate method using diclofenac as a standard drug at a dose of 10 mg/kg body weight and the results were expressed as mean increase in latency after drug administration. The anti-inflammatory activity was evaluated by carrageenaninduced rat paw edema model using indomethacin standard drug at a dose of 10 mg/kg body weight. The results were expressed in terms of mean increase in paw volume – SEM. The extract of the stem bark was given in doses of 250 and 500 mg/kg body weight.
All the doses were administered per orally. results revealed that Oroxylum indicum posseses remarkable analgesic and anti-inflammatory activities. Further studies are needed for isolation of active molecule and establishment of mechanism of action.
Evaluation of analgesic and antipyretic activities of
various leaf extracts of Oroxylum indicum (L.) vent
Background: The ethnobotanical survey and traditional information revealed that the Oroxylum indicum possesses antipyretic, analgesic, anti-inflammatory and diuretic activities.
Aim: The present study was an attempt to investigate the analgesic & antipyretic activity of various extracts of Oroxylum indicum leaves. Methods: The analgesic activity of O. indicum extracts was evaluated on albino mice by tail immersion methods. Whereas antipyretic activity was studied on Brewer’s yeast-induced pyrexia in Wister strain albino rats. All the crude extracts of O. indicum such as petroleum ether, chloroform and ethanol were tested for analgesic and antipyretic activity at 100 and 200 mg/kg body weight. Aspirin (50mg/kg) and Paracetamol (100 mg/kg) were used as standard drugs for analgesic and antipyretic activities respectively.
Results: Among the entire extract pet. ether and ethanol extract shows significant action in a dose of 200 mg/Kg body weight. Whereas ethanol extract in a dose of 200 mg/Kg body weight exhibited significant antipyretic activity after 30 and 45 min as compared to standard paracetamol drug. conclusion: These findings demonstrate that O. indicum leaves have remarkable analgesic and antipyretic activities when compared with positive control and thus have great potential as a source for natural health. The data were verified as statistically significant by using one way ANOVA (analysis of variance) at 5 % level of significance (p<0.05)
Taxonomic and phytomedicinal properties of
Oroxylum indicum (L.) Vent: A wonderful gift of nature
This paper is a review on pharmacological studies, phytochemical analysis and problems associated with natural seed germination of Oroxylum indicum (L.) Vent. The different parts of this plant like leaves, fruits, stem bark, seeds and roots are used in indigenous medicine preparation against various diseases. Chemical investigation of various parts of this plant resulted in characterization of various bioactive principles. It shows antioxidative, antitumour, antiinflammatory, analgesic, antimicrobial and hepatoprotective activity. Due to significant medicinal properties and continuous increasing demand, this plant has been put in endangered category (IUCN)
Paederia scandens (Lour.)Merr extract
Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). The aim of the present study was to investigate the analgesic effect of IGPS on spared nerve injury (SNI) model of neuropathic pain. The SNI model in rats was established by complete transection of the common peroneal and tibial distal branches of the sciatic nerve, leaving the sural branch intact. The mechanical withdrawal threshold (MWT) in response to mechanical stimulation was measured by electronic von Frey filaments on day 1 before operation and on days 1, 3, 5, 7, 10, and 14 after operation, respectively. Nitric oxide synthase (NOS) activity and nitric oxide (NO) production of spinal cord were measured by spectrophotometry and its cyclic guanosine monophosphate (cGMP) content by radioimmunoassay, mRNA expression of inducible NOS (iNOS) and protein kinase G type I (PKG-I, including PKG Ια and PKG Iβ) of spinal cord were analyzed by RT-PCR.
There was a marked mechanical hypersensitivity response observed on day 1 after operation in SNI model, which accompanied with decreased MWT. treatment with IGPS (70, 140, 280 mg/kg) significantly alleviated SNI-induced mechanical hypersensitivity response evidenced by increased MWT; as well as markedly decreased NOS activity, NO and cGMP levels. At the same time, IGPS (70, 140, 280 mg/kg) could also inhibit mRNA expression of iNOS, PKG Ια and PKG Iβ in the spinal cord.
The results suggested that IGPS possesses antinociceptive effect, which may be partly related to the inhibition of NO/cGMP/PKG signaling pathway in the rat SNI model of neuropathic pain.
Anti-nociceptive activity of aqueous fraction from the MeOH extracts of Paederia scandens in mice
Aim of the study: We examined the effects of the aqueous fraction (AF) on nociception models mice induced by the chemical and the thermal stimuli so as to elucidate the analgesic activity and provide scientific basis for the clinical use of Paederia scandens.
Materials and Methods: The AF of MeOH extract from P. scandens was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception.
Results: Given orally, the aqueous fraction at doses of 200, 400 and 800 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin injections and on thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at dose of 800 mg/kg of this fraction. In the pentobarbital sodium –induced sleeping time test and the open-field test, the aqueous fraction neither significantly enhanced the pentobarbital sodium –induced sleeping time nor impaired the motor performance, indicating that the observed anti-nociception was unlikely due to sedation or motor abnormality.
Conclusions: These results suggested that the aqueous fraction produced anti-nociception possibly related to the iridoid glycosides and polysaccharides in this fraction.
The petroleum ether fraction of MeOH extract from Paederia scandens was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception. Given orally, the petroleum ether fraction (PEF) at doses of 20, 40 and 80 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at dose of 80 mg/kg of the petroleum ether fraction. In the pentobarbital sodium-induced sleeping time test and the open-field test, the petroleum ether fraction neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-nociception was unlikely due to sedation or motor abnormality.
Moreover, the petroleum ether fraction–induced anti-nociception in both capsaicin and formalin tests was insensitive to naloxone, but was significantly antagonized by glibenclamide. These results suggested that the petroleum ether fraction produced anti-nociception possibly related to glibenclamide-sensitive K+-ATP channels, which merited further studies regarding the precise site and mechanism of action. The major constituents of the petroleum ether fraction (PEF) determined by GC/MS analysis, are linoleic acid, the sterols and vitamin E. Therefore it can be suggested that they exert synergetic effects and are together responsible for the antinociceptive activity of the PEF-fraction.
Paeonia lactiflora Pall. root extract
mechanisms involved in the therapeutic effects of Paeonia lactiflora Pallas in rheumatoid arthritis
Paeonia lactiflora Pallas, also named Chinese Paeony, is a Chinese herb. A decoction of its root has been used to treat painful or inflammatory disorders in traditional Chinese medicine. A water/ethanol extract of Radix Paeoniae is known as total glycosides of paeony (TGP), of which paeoniflorin is the major active component. Preclinical studies show that TGP/paeoniflorin is able to diminish pain, joint swelling, synovial hypertrophy, and the severity of bone erosion and cartilage degradation in experimental arthritis. TGP/paeoniflorin suppresses inflammatory process by reducing the production of prostaglandin E2, leukotriene B4, nitric oxide, reactive oxygen species, proinflammatory cytokines and chemokines. TGP/paeoniflorin also inhibits the proliferation of lymphocytes and fibroblast-like synoviocytes, the formation of new blood vessels, and the production of matrix metalloproteinases.
Clinical data show that TGP is effective to relieve the symptoms and signs of rheumatoid arthritis without significant adverse effects. Recently, TGP is widely used to treat rheumatoid arthritis in China.
Paeoniflorin (PF) is one of the principle active ingredients of the root of Paeonia lactiflora Pall (family Ranunculaceae), a Chinese herb traditionally used to relieve pain, especially visceral pain. The present study aimed to investigate both the effect of PF on neonatal maternal separation–induced visceral hyperalgesia in rats and the mechanism by which such effect is exerted. A dose-dependent analgesic effect was produced by PF (45, 90, 180, and 360 mg/kg i.p.). Centrally administered PF (4.5 mg/kg i.c.v) also produced a significant analgesic effect. The analgesic effect of PF (45 mg/kg i.p.) was maximal at 30 minutes after administration. Furthermore, it was found that nor-binaltorphimine (nor-BNI, 3 mg/kg i.p.), dl-α-methyltyrosine (α-AMPT, 250 mg/kg i.p.), and yohimbine (3 mg/kg i.p.) could block the analgesic effect of PF (45 mg/kg i.p.). Time course determination of PF in brain nuclei showed that the maximal concentration of PF was 30 minutes after intraperitoneal administration of PF (180 mg/kg) in cerebral nuclei, involving the amygdala, hypothalamus, thalamus, and cortex. These data indicate that PF has an analgesic effect on visceral pain in rats with neonatal maternal separation and that this effect may be mediated by κ-opioid receptors and α2-adrenoceptors in the central nervous system.
This study demonstrates that PF has an analgesic effect on pain in visceral hyperalgesic rats. These results suggest that PF might be potentially useful in clinical therapy for irritable bowel syndrome as a pharmacological agent in alleviating visceral pain.
In China, Korea, and Japan, a decoction of the dried root without bark of Paeonia lactiflora Pall. has been used in the treatment of rheumatoid arthritis, systemic lupus erythematosus, hepatitis, dysmenorrhea, muscle cramping and spasms, and fever for more than 1200 years. A water/ethanol extract of the root is now known as total glucosides of peony (TGP), which contains more than 15 components. Paeoniflorin is the most abundant ingredient and accounts for the pharmacological effects observed with TGP in both in vitro and in vivo studies. The analgesic effect of TGP was confirmed in various animal models of pain, which may be mediated partly by adenosine A1 receptor. The direct anti-inflammatory effects of TGP were observed in animal models of both acute and subacute inflammation, by inhibiting the production of prostaglandin E2, leukotriene B4, and nitric oxide, and by suppressing the increase of intracellular calcium ion concentration. TGP was also reported to have protective effects of cells against oxidative stress. In vitro, dual effects of TGP were noted on the proliferation of lymphocytes, differentiation of Th/Ts lymphocytes, and the production of proinflammatory cytokines and antibodies. In vivo, TGP inhibited the delayed-type hypersensitivity in immuno-activated mice, and enhanced the delayed-type hypersensitivity in immuno-suppressed mice. In adjuvant arthritis rats, paeoniflorin exerted immunosuppressive effects. The beneficial effects of TGP in treating rheumatoid arthritis were verified by randomized controlled trials. The adverse events of TGP were mainly gastrointestinal tract disturbances, mostly mild diarrhea.
Paeoniae Radix is one of the most well-known herbs in China, Korea, and Japan for more than 1200 years. Paeonies are divided into two groups: the tree Peony (also named Paeonia Moutan) and the herbaceous kinds. Paeonia lactiflora Pall. (also named Chinese Peony) is a herbaceous perennial flowering plant in the family Paeoniaceae with fleshy roots and annual stems. It is about 60–100 cm tall with large compound leaves 20–40 cm long. The flower buds are large and round, opening into large flowers 8–16 cm diameter, with 5–10 white, pink, or crimson petals and yellow stamens (Figure 1). It is native to east Asia, and is grown on dry open stony slopes, riverbanks and sparse woodland edges.
Papaver libanoticum extract
Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae) that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE) using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome.
passion fruit peel extract
Knee osteoarthritis (OA) is a common degenerative joint disorder and a major cause of pain and disability. The hypothesis tested in this study was that the passion fruit peel extract (PFP), a flavonoid-rich dietary supplement, would reduce symptoms due to knee OA. Thirty-three OA patients were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Patients received either placebo or PFP pills (150 mg, daily) in a double-blinded fashion for 2 months. The OA clinical symptoms were evaluated monthly with Western Ontario and McMaster Universities (WOMAC) osteoarthritis Index. In the PFP group, there was a significant improvement in total WOMAC score and WOMAC subscale score of physical function after 30 days and pain after 60 days. At 60 days, reductions of 18.6%, 18%, 19.6%, and 19.2% in pain, stiffness, physical function, and composite WOMAC score, respectively, were self-reported in the PFP group. Whereas, in the placebo group, the self-reported WOMAC scores increased in every category. The results of this study show that PFP substantially alleviated osteoarthritis symptoms. This beneficial effect of PFP may be due to its antioxidant and antiinflammatory properties.
Perilla frutescens (L.) Britt. extract
Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of inflammation and osteoarthritis. And nitric oxide (NO) activated the MMPs responsible for PG degradation in articular chondrocytes. Therefore, we have studied the effects on anti-inflammation and analgesic by ethyl acetate fraction from 70% ethanol extract of Perilla Frutescens (EPF). EPF inhibited LPS plus inflammation–cytokines–induced proteoglycan (PG) degradation, matrix-metalloproteinase (MMP-2,9) expression in rabbit articular chondrocytes. Also, EPF have inhibitory effects on LPS or LPS plus inflammation cytokines–induced nitric oxide (NO) and PGE2 production in mouse macrophage andrabbit articular chondrocytes.
These results suggest that EPF decreases PGE2, iNOS, MMPs activity and PG degradation in mouse macrophage and/or rabbit articular chondrocytes. In vivo, EPF was shown to have inhibitory effects on acetic acid-induced pain. The herbal extract with this profile, may have utility in the treatment of osteoarthritis.
Perilla frutescens fruit oil (PFO) is rich in α-linolenic acid (ALA) and exhibits biological activities. We aimed to investigate analgesic, anti-inflammatory and anti-ulcer activities of PFO and PFO-supplemented soybean milk (PFO-SM) in animal models. analgesic activity was assessed in acetic acid-induced writhing in mice, while anti-inflammatory activity was performed in ethyl phenylpropiolate (EPP)-induced ear edema and carrageenan-induced hind paw edema in rats. Anti-ulcer effects were conducted in water immersion stress, HCl/ethanol and indomethacin-induced gastric ulcer in rats. Distinctly, PFO, containing 6.96 mg ALA and 2.61 mg LA equivalence/g, did not induce acute toxicity (LD50 > 10 mL/kg) in mice. PFO (2.5 and 5 mL/kg) and PFO-SM (0.05 mL PFO equivalence/kg) inhibited incidences of writhing (16.8, 18.0 and 32.3%, respectively) in acetic acid-induced mice. In addition, topical applications of PFO (0.1 and 1 mL/ear) significantly inhibited EPP-induced ear edema (59.3 and 65.7%, respectively) in rats, while PFO-SM slightly inhibited ear edema (25.9%).
However, PFO and PFO-SM did not inhibit carrageenan-induced hind paw edema in rats. Indeed, PFO (2.5 and 5 mL/kg) significantly inhibited gastric ulcers in rats that induced by water immersion stress (92.4 and 96.6%, respectively), HCl/ethanol (74.8 and 73.3%, respectively) and indomethacin (68.8 and 88.9%, respectively), while PFO-SM did not. PFO displayed potent analgesic, anti-inflammatory and anti-ulcer properties, while PFO-SM exerted only analgesic properties. Thus, Thai PFO and its functional drink offer potential benefits in treatment of analgesic, inflammatory diseases and gastric ulcer.
Phoenix sylvestris
Diuretic and analgesic effects of the methanol extract of Phoenix sylvestris root.
The analgesic and diuretic activities of the methanol extract of Phoenix sylvestris root on Swiss albino mice were observed. The extract showed significant (p<0.001) analgesic activity by reduction of percent inhibition of writhing induced by acetic acid (0.5% v/v) in 20.07% and 32.57% at a dose level of 150 mg/kg and 300-mg/kg body weights respectively.
The methanol extract also showed diuretic effect at 1st hour of the study at 300-mg/kg and 2nd and 4th hour of the study at 150-mg/kg-body weight on swiss albino mice. The onset of diuretic effect was faster at a dose of 300-mg/kg body weights than 150 mg/kg body weight. The obtained results may give a clue for extensive phytochemical investigation of the plant for the development of herbal medicine.
Phyllanthus amarus
This study investigated the anti-allodynic and anti-oedematogenic effects of the hexanic extract, lignan-rich fraction and purified lignans from a plant used in the traditional medicine, Phyllanthus amarus, in the inflammatory and neuropathic models of nociception. The hexanic extract inhibited the allodynia and the oedema induced by the intraplantar injection of complete Freund’s adjuvant (CFA). The inhibition observed was 76±7% (ipsilateral paw), 64±7% (contralateral paw), and 41±2% (oedema). Otherwise, the lignan-rich fraction or the pure lignans did not affect CFA-induced allodynia. Administered chronically, the lignan fraction reduced CFA-induced paw oedema (39±9%). When evaluated in the model of neuropathic pain caused by partial ligation of sciatic nerve, the hexanic extract inhibited the mechanical allodynia (77±7%), with a similar efficacy to the gabapentin (71±10%). The anti-allodynic effects of hexanic extract of P. amarus seem not to be associated with the impairment of motor co-ordination or with the development of tolerance.
Finally, the treatment with hexanic extract inhibited the increase of myeloperoxidase activity, either following intraplantar injection of CFA or after sciatic nerve injury. It is concluded that, apart from its anti-inflammatory actions, which are probably linked to the presence of lignans, another as yet unidentified active principle(s) present in the hexanic extract of P. amarus produces pronounced anti-allodynia in two models of inflammatory and neuropathic pain. Considering that few drugs are currently available for the treatment of chronic pain, especially of the neuropathic type, the present results may have clinical relevance and open new possibilities for the development of new anti-allodynic drugs.
Phyllanthus corcovadensis
potent antinociceptive activity of a Hydroalcoholic extract of Phyllanthus corcovadensis
This study analyses the analgesic effect of a hydroalcoholic extract (HE) from Phyllanthus corcovadensis in several models of pain in mice. HE (3–60 mg kg−1, i.p.) or (100–500 mg kg−1, p.o.) caused a graded and potent analgesic effect against the abdominal constriction response caused by acetic acid and acetylcholine with an ID50 of about 3 and 100 mg kg−1, respectively. In the tail-flick model HE (up to 500 mg kg−1, p.o.) was without effect, while morphine (1–10 mg kg−1, s.c.) caused a graded increase in pain latency (ID50, 3 mg kg−1). HE (1–300 mg kg−1) given both intraperitoneally and orally caused a potent and graded inhibition of the second phase of formalin-induced persistent pain in mice with an ID50 of 1 and 80 mg kg−1, respectively. In contrast, morphine (1–5 mg kg−1, s.c.) inhibited both phases of formalin-induced pain with an ID50 of 2·5 mg kg−1. Indomethacin (1–10 mg kg−1, i.p.) only inhibited the second phase of formalin-induced pain with an ID50 of about 3 mg kg−1. The analgesic effect of indomethacin, but not that caused by morphine and HE was accompanied by a graded inhibition of formalin-induced mouse paw oedema. In addition, HE up to 1 g kg−1 failed to prevent carrageenan- and dextran-induced rat hindpaw oedema.
It is concluded that HE exhibits a potent antinociceptive profile, either when given intraperitoneally or orally. The mechanisms that underly its analgesic effect are unclear at present, but appear to be unrelated to inhibition of synthesis of arachidonic acid via cyclo-oxygenase or to activation of opioid receptors.
analgesic effects of Callus Culture extracts from Selected Species of Phyllanthus in Mice
Abstract— The aim of this study was to evaluate the analgesic effect of the methanolic extract from callus culture of Phyllanthus tenellus, P. corcovadensis and P. niruri in several models of pain in mice. The extracts (medium containing 2,4-dichlorophenoxyacetic acid) of P. corcovadensis, P. niruri and P. tenellus (3–90 mg kg−1, i.p.) caused graded inhibition of abdominal constrictions induced by acetic acid (0·6%), with ID50 (i.e. dose that reduced response of control by 50%) values of about 30, 19 and >30 mg kg−1, respectively. The extract of callus of Phyllanthus obtained in indole-3-butyric acid and indole-3-acetic acid media (3–90 mg kg−1, i.p.) caused a similar analgesic effect. In the formalin test, the extract of P. tenellus obtained in indole butyric acid medium (3–100 mg kg−1, i.p.) inhibited only the second phase of formalin-induced pain with an ID50 value of about 100 mg kg−1.
Both the indole acetic acid and indole butyric acid methanolic extracts of P. tenellus and P. corcovadensis (10–100 mg kg−1, i.p.) dose-dependently inhibited both phases of formalin-induced pain (ID50 values for the second phase were approx. 100 and 52 mg kg−1, respectively). However, the extract of callus from Phyllanthus failed to affect formalin-induced paw oedema, as well as the response to radiant heat in the tail-flick test. In addition, the analgesic effect of morphine, but not the analgesic effects caused by Phyllanthus callus extract, was fully antagonized by naloxone. Preliminary phytochemical analysis revealed the presence of several compounds having no apparent relationship with alkaloids or flavonoids but showing the presence of phenols.
These results indicate that, similar to previous reported data from the extract of P. corcovadensis, the methanolic extracts of callus culture of P. niruri, P. corcovadensis and P. tenellus exhibit potent analgesic properties against neurogenic and inflammatory pain that seem to be unrelated to the activation of opioid mechanisms.
Phyllanthus niruri
analgesic effects of Callus Culture extracts from Selected Species of Phyllanthus in Mice
The aim of this study was to evaluate the analgesic effect of the methanolic extract from callus culture of Phyllanthus tenellus, P. corcovadensis and P. niruri in several models of pain in mice. The extracts (medium containing 2,4-dichlorophenoxyacetic acid) of P. corcovadensis, P. niruri and P. tenellus (3–90 mg kg−1, i.p.) caused graded inhibition of abdominal constrictions induced by acetic acid (0·6%), with ID50 (i.e. dose that reduced response of control by 50%) values of about 30, 19 and >30 mg kg−1, respectively. The extract of callus of Phyllanthus obtained in indole-3-butyric acid and indole-3-acetic acid media (3–90 mg kg−1, i.p.) caused a similar analgesic effect. In the formalin test, the extract of P. tenellus obtained in indole butyric acid medium (3–100 mg kg−1, i.p.) inhibited only the second phase of formalin-induced pain with an ID50 value of about 100 mg kg−1. Both the indole acetic acid and indole butyric acid methanolic extracts of P. tenellus and P. corcovadensis (10–100 mg kg−1, i.p.) dose-dependently inhibited both phases of formalin-induced pain (ID50 values for the second phase were approx. 100 and 52 mg kg−1, respectively).
However, the extract of callus from Phyllanthus failed to affect formalin-induced paw oedema, as well as the response to radiant heat in the tail-flick test. In addition, the analgesic effect of morphine, but not the analgesic effects caused by Phyllanthus callus extract, was fully antagonized by naloxone. Preliminary phytochemical analysis revealed the presence of several compounds having no apparent relationship with alkaloids or flavonoids but showing the presence of phenols.
These results indicate that, similar to previous reported data from the extract of P. corcovadensis, the methanolic extracts of callus culture of P. niruri, P. corcovadensis and P. tenellus exhibit potent analgesic properties against neurogenic and inflammatory pain that seem to be unrelated to the activation of opioid mechanisms.
Phyllanthus tenellus
analgesic effects of Callus Culture extracts from Selected Species of Phyllanthus in Mice
Abstract— The aim of this study was to evaluate the analgesic effect of the methanolic extract from callus culture of Phyllanthus tenellus, P. corcovadensis and P. niruri in several models of pain in mice. The extracts (medium containing 2,4-dichlorophenoxyacetic acid) of P. corcovadensis, P. niruri and P. tenellus (3–90 mg kg−1, i.p.) caused graded inhibition of abdominal constrictions induced by acetic acid (0·6%), with ID50 (i.e. dose that reduced response of control by 50%) values of about 30, 19 and >30 mg kg−1, respectively. The extract of callus of Phyllanthus obtained in indole-3-butyric acid and indole-3-acetic acid media (3–90 mg kg−1, i.p.) caused a similar analgesic effect. In the formalin test, the extract of P. tenellus obtained in indole butyric acid medium (3–100 mg kg−1, i.p.) inhibited only the second phase of formalin-induced pain with an ID50 value of about 100 mg kg−1. Both the indole acetic acid and indole butyric acid methanolic extracts of P. tenellus and P. corcovadensis (10–100 mg kg−1, i.p.) dose-dependently inhibited both phases of formalin-induced pain (ID50 values for the second phase were approx. 100 and 52 mg kg−1, respectively).
However, the extract of callus from Phyllanthus failed to affect formalin-induced paw oedema, as well as the response to radiant heat in the tail-flick test. In addition, the analgesic effect of morphine, but not the analgesic effects caused by Phyllanthus callus extract, was fully antagonized by naloxone. Preliminary phytochemical analysis revealed the presence of several compounds having no apparent relationship with alkaloids or flavonoids but showing the presence of phenols. These results indicate that, similar to previous reported data from the extract of P. corcovadensis, the methanolic extracts of callus culture of P. niruri, P. corcovadensis and P. tenellus exhibit potent analgesic properties against neurogenic and inflammatory pain that seem to be unrelated to the activation of opioid mechanisms.
Piper betle L. leaves
The leaves of Piper betle L. (Piperaceae) are widely chewed in Bangladesh as betel quid with or without tobacco. Chewing of leaves of the plant is advised by the folk medicinal practitioners of Bangladesh to alleviate pain (particularly toothache) and lowering of blood sugar, as well as aid the digestive process. The objective of this study was to scientifically evaluate the folk medicinal practitioner’s claims of the antihyperglycemic and antinociceptive properties of Piper betle leaves. Antihyperglycemic activity evaluation was conducted through oral glucose tolerance tests in glucose-loaded Swiss albino mice, while antinociceptive activity tests were performed in gastric pain models in Swiss albino mice, where gastric pain was induced by intraperitoneal administration of acetic acid. In antihyperglycemic activity tests, methanolic extract of leaves demonstrated dose-dependent and significant lowering of blood sugar in glucose-challenged mice. At extract doses of 50, 100, 200 and 400 mg per kg body weight, prior oral administration of the extract reduced blood sugar levels by 31.01, 34.38, 38.88 and 46.74%, respectively, as compared to control animals. A standard antihyperglycemic drug, glibenclamide, when orally administered at a dose of 10 mg per kg body weight lowered blood glucose levels by 46.07%. As such, the results strongly indicate that leaves of the plant possess potent antihyperglycemic properties.
In antinociceptive activity tests, the methanolic extract of the leaves significantly and dose-dependently reduced the number of gastric writhings in gastric pain–induced mice. At doses of 50, 100, 200 and 400 mg extract per kg body weight, the percent reductions in writhings were, respectively, 47.00, 63.28, 69.40 and 71.48 as compared to control mice. The standard antinociceptive drug, aspirin, when administered at doses of 200 and 400 mg per kg body weight, reduced the number of writhings by 51.04 and 67.32%, respectively. The extract, therefore, appears to be more potent than aspirin in alleviation of pain.
Overall, the results validate the folk medicinal uses of the leaves of this plant and suggest that more scientific researches need to be carried out on isolation and identification of the relevant bioactive components present within the leaves of this plant.
Piper longum L.extract
preventive potentials of piperlongumine and a Piper longum extract against stress responses and pain
Aim
To compare stress resistance increasing and analgesic activities of piperlongumine and a methanolic Piper longum fruit extract (PLE).
Methods
Efficacies of a single and repeated daily oral doses (1–256 mg/kg/day) of PLE, piperlongumine, and 50 mg/kg/day doxycycline against foot shock stress triggered alteration in body weights and core temperatures, and of their 11 daily doses on antidepressants like activity in tail suspension test and on pentobarbital induced sedation in male mice were compared. In another experiment, analgesic activities of single and repeated daily 5 mg/kg oral doses of piperlongumine and PLE in mice hot plate test and in acetic acid induced writing tests were compared with those of aspirin and doxycycline.
results
After their single oral doses no effects of piperlongumine or PLE or doxycycline were observed in the footshock stress induced hyperthermia test or in hot plate test. However, significant effects of piperlongumine and PLE in both the tests were observed after their 5 or more daily doses. Both of them also dose dependently suppressed daily handling and repetitive testing triggered alterations in body weights and core temperatures. Their doxycycline like antidepressant activity in tail suspension test and aspirin like analgesic effects in acetic acid writhing test were observed after their 11 daily 5 mg/kg oral dose.
conclusion
Piperlongumine is another bioactive secondary metabolite of P. longum and other plants of piper species with stress response suppressing, analgesic, and anti-inflammatory activities. Its bactericidal activities can also contribute to its therapeutically interesting bio-activity profile.
analgesic and anti-inflammatory activities of Piper nigrum L.
Objective: To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats.
Methods: The analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats.
Results: Piperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min.
Conclusions: It is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities.
Objective: essential oils are complex mixtures of chemical compounds, extracted from a wide range of plants. The volatile fraction of essential oils is responsible for their characteristic aroma and presents diverse biological properties that have been studied over the years. In Traditional Chinese medicine, Piper nigrum is considered to be pungent and hot. Although its chemical constituents and respective pharmacological properties have been described by several authors, the volatile fraction is still underestimated as a therapeutic agent. The aim of this study was to evaluate the analgesic properties of the volatile fraction of Piper nigrum essential oil, in patients presenting different types of pain.
Methods: Fifty-four patients presenting pain, were included in a randomized, double-blind, placebo-controlled study, over a 9-week period. The patients were randomly divided into two groups, and asked to inhale a vial containing Piper nigrum essential oil, or a vial containing a placebo (sesame oil), for 15 minutes. A numerical pain scale was applied before and after the inhalation.
Results: results showed a statistically significant decrease in pain intensity in the patients that inhaled the black pepper essential oil, while the placebo group patients showed no significant change in pain intensity.
Conclusion: Although the results are preliminary due to the limited sample size and short inhalation time, the volatile fraction of the Piper nigrum essential showed promising results in reducing pain. In the Chinese medicine perspective, these results support the use of black pepper in different types of pain, since it warms the center and disperses cold.
Pepper as analgesic and anti-inflammatory Alternative and Bio-enhancer agent for treatment of pain
Pain is considered as an unpleasant distressing feeling in different parts of body in response to different stimuli. The use of opioids, narcotic and non-narcotic drugs is associated with adverse effects; therefore, research on natural analgesics has been the subjects of many investigations. Due to the traditional importance of Piper nigrum in management of pain, the subject of this article was to evaluate the potency of P. nigrum in pain. The electronic sources (PubMed, Science Direct, Wiley, Springer, etc.) were used to prepare the manuscript by the key words of “black pepper”, “Piper nigrum” and “pain”.
The results of different animal studies confirmed that among different species of pepper, P. nigrum or P. longum significantly reduced the severity of pain and their analgesic potencies were mediated by piperine, which induced the inhibition of inflammatory cytokines and prostaglandin E2 or activation of calcium influx. Although piperine is found as analgesic compounds in pepper, but other components such as piperlongumine or essential oil enhanced their analgesic effects. P. nigrum, P. longum or piperine is one ingredient of analgesic formulates in combination with Zingiber officinale or Curcuma longa in human clinical studies. Therefore, formulate consists of piperine or P. nigrum in combination with analgesic herbs including Z. officinale, curcumin or ASU blend can be the subject of further clinical studies.
Pleurotus eous mushroom
Objective: To evaluate the analgesic activity of the ethyl acetate, methanol and aqueous extracts of Pleurotus eous (P. eous) mushroom.
Methods: The dried fruiting bodies were extracted with ethyl acetate, methanol and water. The analgesic effect of extracts of P. eous were investigated at doses 250 500 and 1 000 mg/kg body weight, using acetic-acid induced writhing, hot-plate, tail immersion and tail-clip tests.
Results: P. eous extracts produced significant reduction in number of writhes induced by intraperitoneal injection of acetic-acid (P<0.05). Moreover, in hot-plate and tail immersion test, all the three extracts significantly raised the pain threshold at different time of observation (0-60 min) in comparison with control (P<0.05). In tail-clip test the extracts also caused a significant inhibition of pain at both the doses used (P<0.05).
Conclusions: The results of present study suggest that extracts of P. eous possess potent analgesic property and could serve as a base for future drugs.
Polygala anatolica Boiss. et Heldr
Polygala anatolica Boiss. et Heldr.:
Is A potential remedy for inflammation and pain?
Species of Polygala genus have been used for the treatment of inflamation and pain in Turkish traditional medicine. The aim of the present study is to assess the anti-inflammatory and analgesic activities of P. anatolica. n-Hexane, ethyl acetate and methanol extracts of the aerial parts and roots of P. anatolica were investigated for their anti-inflammatory and analgesic effects. The methanol extracts prepared from the aerial parts and roots of P. anatolica were found to be active in carrageenan- and PGE2-induced paw edema models and in Whittle method. Methanolic extract of the aerial part inhibited serotonin-induced hind paw edema, while the root extract did not exert inhibitory effect in the same model. In addition, Fr. B and C obtained from the methanol extract of P. anatolica aerial parts showed significant anti- inflammatory activity.
Morover, the analgesic effect of the methanol extracts prepared from the roots and aerial parts and Fr.B and Fr.C were found to be statistically significant without inducing ulceration. The methanol extract obtained from the aerial parts of the plant and its saponoside and flavonoid fractions showed anti-inflammatory and analgesic activities in the trials.
Polygala jaPonica Houtt. extract
This study was to investigate the anti-inflammatory and analgesic activities of the total saponins extracted from fermented Polygala japonica Houtt (FPH) compared with that of unfermented Polygala japonica Houtt (UFPH). The total saponins extracted from FPH and UFPH were evaluated for anti-inflammatory activity in xylene-induced ear swelling and acetic acid-induced vascular permeability models in mice, analgesic activity in acetic acid-induced writhing and hot plate models in mice. The total saponins extracted from FPH had the significant anti-inflammatory (p<0.001) and analgesic (p<0.01) activities with the doses of 6 g/kg b.w. in mice.
The results of this experimental study thus strongly support the potential significant use of the total saponins extracted from FPH for pain and inflammatory.
Polygonum cuspidatum Sieb. et Zucc root extract
Polygonum cuspidatum (PC) has been used for the treatment of arthritis and urinary diseases in traditional medicine. Despite recent evidence that PC has anti-oxidant, anti-tumoral, and anti-inflammatory effects, analgesic and anti-inflammatory effects of PC have not been elucidated yet in vivo. Thus, in the present study, analgesic and anti-inflammatory effects of ethyl acetate extract of PC (EAPC) were investigated in vivo for the first time. Hot plate test and tail-flick test revealed that EAPC at 200 mg/kg exerts analgesic effect (p < 0.05). In contrast, EAPC did not show significant analgesic effect in acetic acid–induced writhing test. Serotonin-induced paw edema model and Freund’s complete adjuvant (FCA)–induced adjuvant arthritis model were used to examine anti-inflammatory effect of EAPC in vivo. In serotonin-induced paw edema model, EAPC suppressed swelling inflammatory response within 12 min after serotonin injection, at both 100- and 200-mg/kg dose (p < 0.05).
Consistently, in FCA-induced adjuvant arthritis model, FCA at 200 mg/kg significantly suppressed FCA-induced joint swelling within 3 days (p < 0.05), whereas FCA at 100 mg/kg showed the similar result within 5 days (p < 0.05). Furthermore, EAPC effectively inhibited positive responses of c-reactive protein and rheumatoid factor compared to untreated control. Taken together, our findings suggest that EAPC can be a potent candidate for rheumatoid arthritis treatment.
Background: Chronic pain is frequently comorbid with anxiety disorder, thereby complicating its treatment. Polydatin, a component from the root of Polygonum cuspidatum, has shown neuro protection in the central nervous system. However, its effects on pain and anxiety processing have been rarely investigated. In this study, mice were injected with complete Freund’s adjuvant (CFA) at the hindpaw to induce pain– and anxiety-like behaviors.
Results:treatment with polydatin (25 mg/kg) alleviated the anxiety-like behaviors but not pain perception in these mice. Polydatin treatment reversed the upregulation of N-methyl-D-aspartic acid receptors and GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors in the amygdala of CFA-injected mice. Additionally, this treatment reduced the levels of proinflammatory cytokines, namely, tumor necrosis factor-alpha and interleukin-1β, in the amygdala. Furthermore, activated nuclear factor kappa-B signaling was blocked in the amygdala from CFA-injected mice. By using docking technology, we found potential structural binding between polydatin and IκB kinase beta.
Conclusion:This study indicates the anxiolytic effects of polydatin by suppressing inflammatory cytokines in the amygdala.
Polyphylla Paris Rhizome extract
Abstract: The antinociceptive and anti-inflammatory effects of the extract of aerial parts and rhizome of Paris polyphylla var. chinensis were evaluated to find active fractions.The hot plate test,thermal radiation pain test and acetic acid-induced mouse writhing test were used to assess the anti-nociceptive effect and xylene-induced mouse ear edema was conducted to assess the anti-inflammatory effect of the extract,fractions and sub-fractions (furostanol saponin,pennogenin saponin and dioscin saponin).
The results showed that the rhizome extract displayed the significant anti-nociceptive effects:the extract at the dose of 2.4 g crude material·kg-1 showed significant anti-nociceptive effect in the hot plate test,while the extract at the doses of both 0.6 and 2.4 g crude material·kg-1 displayed significant anti-nociceptive effect in the thermal radiation pain test.The extract at all doses of (0.3,0.6 and 2.4 g crude material·kg-1）displayed significant anti-nociceptive effect in a dose-dependent manner in the writhing test.The extract significantly inhibited the mouse ear edema induced by xylene in a dose-dependent manner.The extract of aerial parts showed the similar anti-nociceptive and anti-inflammatory effect as those of rhizome.The anti-inflammatory effect of aerial parts and rhizome are attributed to the steroidal saponins enriched in the fractions eluted by 50%,70% and 95% ethanol on macroporous resin chromatography.
All sub-fractions (furostanol,pennogenin and dioscin saponin) demonstrated the potent anti-inflammatory effect,and among them,pennogenin saponins have the strongest activity.The present investigation provided some evidences for the development of quality evaluation system concerning the traditional efficacy of Paridis rhizoma and the comprehensive utilization of the aerial parts of Paris polyphylla var. chinensis.
Objectives: The analgesic and hemostatic effects of Paris polyphylla, Scutellaria baicalensis, and their compatibility were studied.
Methods: In the experiment on the writhing of mice induced by acetic acid, 60 Kunming SPF mice were randomly selected, and were randomly divided into 6 groups according to the male-to-female ratio of 1∶1, including blank control group, P. polyphylla group, S. baicalensis group, and three P. polyphylla and S. baicalensis compatibility groups（with the ratio of 1∶2, 1∶1 and 1∶2）. There were 10 mice in each group. In the experimental groups, the mice were given 1 g/mL Chinese medicine extract according to a dose of 20 mL/kg. In the control group, the mice were given 0.9% normal saline in equal volumes. Gavage was performed one time every 24 h and lasted for 14 d. 1 h after the gavage on the 14 th day, they were given 0.5% glacial acetic acid solution via intraperitoneal injection. In the hot plate experiment, 60 Kunming SPF mice were selected, and the ratio of male to female, grouping, administration and gavage were the same as those of the glacial acetic acid-induced writhing experiment. Gavage was lasted for 14 d. 1 h after the gavage on the 14 th day, the mice were placed on a hot plate apparatus at（55±0.5） ℃, and the time of licking hindfoot was measured. The hemostatic effect was explored through three experimental methods of tail hemostasis, femoral artery hemostasis and liver hemostasis. 60 Kunming SPF mice were taken in each of the three experiments, and the male-female ratio and grouping were the same as above. The powder was covered on the surface of the wound sites, and the bleeding was observed. The hemostatic time was recorded, and the hemostatic time was recorded as 3 min if it exceeded 3 min.
Results: In the acetic acid-induced writhing experiment, compared with the blank control group, the pain of mice in the experimental groups was inhibited. Among them, P. polyphylla group, S. baicalensis group, compatibility 1∶2 group, compatibility 1∶1 group, and compatibility 2∶1 group had significant effects（P<0.05）, and the inhibition rate of writhing was 20.43%, 28.32%, 52.30%, 32.79 %, and 39.02%, respectively. The analgesic effect of the compatibility 1∶2 group was the most obvious. In the hot plate experiment, compared with the blank control group, the experimental groups had analgesic effect. Among them, P. polyphylla group, S. baicalensis group, compatibility 1∶2 group, compatibility 1∶1 group, and compatibility 2∶1 group had significant effects（P<0.05）, and the increase rate of pain threshold was 29.17%, 47.83%, 61.54%, and 50.61%, and 53.83%, respectively. The analgesic effect of the compatibility 2∶1 group was the most significant. In the hemostatic experiment, there was a significant difference in hemostatic time between the compatibility 1∶2 group and the blank control group, P. polyphylla group, and S. baicalensis group (P<0.05). The hemostatic effect of the compatibility 1∶2 group was the best.
Conclusions: P. polyphylla, S. baicalensis, and its compatibility had good analgesic and hemostatic effects, and the best compatibility ratio was 1∶2.
Propolis
natural Products: Anti-hyperalgesic effect of an Ethanolic extract of Propolis in Mice and Rats
Propolis, or bee glue, which contains a complex mixture of secondary metabolites, has long been used in many countries for the management of several diseases. The purpose of this study was to evaluate, by means of several pharmacological models, the anti-hyperalgesic effect of propolis collected in the south of Brazil.
The abdominal constrictions induced in mice by intraperitoneal injection of acetic acid (0.6%), kaolin (50 mg kg−1) or zymosan (40 mg kg−1) were inhibited to different extents by an extract of propolis (1–60 mg kg−1) administered intraperitoneally 30 min earlier; mean ID50 (concentrations resulting in 50% inhibition) values were 2.7, 10.8 and 10.7 mg kg−1, respectively, and maximum inhibition was 58 ± 5, 57 ± 10 and 51 ± 5%, respectively. Given orally (25–200 mg kg−1, 1 h previously) propolis also inhibited the abdominal constrictions induced by acetic acid (maximum inhibition 43 ±5%).
When injected intraperitoneally (3–60 mg kg−1, 30 min previously), propolis attenuated both the neurogenic (first phase) and inflammatory (second phase) pain responses and paw oedema caused by intraplantar injection of formalin (2.5%); maximum inhibition was 32 ±5, 43 ±6 and 19 ±2%, respectively. oral administration of propolis (25–200 mg kg−1, 1 h previously) inhibited both phases and reduced the oedema formation associated with the second phase of the formalin test (maximum inhibition 22±5, 33 ±6 and 26±3%) and extract of propolis (3–30 mg kg−1 i.p. or 25–100 mg kg−1 p.o., respectively 30 min and 1 h previously) significantly inhibited capsaicin-induced pain with maximum inhibition of 39±8 and 41 ±8%, respectively.
When assessed in the Randall–Sellito test of pain, the extract of propolis (3–30 mg kg−1, i.p., 30 min previously) significantly reversed the hyperalgesia induced by intraplantar injection of bradykinin (3 nmol per paw) in rats (P < 0.01). In contrast with morphine the extract of propolis (. 100 mg kg−1, 30 min previously) was ineffective when assessed in the tail-flick and hot-plate thermal assays. Naloxone (5 mg kg−1 i.p.) reversed (P < 0.01) the effect of morphine (5 mg kg−1 s.c.) by 70 and 94% respectively in the first and second phases of the formalin test, but did not interfere with the analgesic effect of propolis (10 mg kg−1 i.p., 30 min previously).
These results show that ethanolic extract of propolis, given systemically, has significant anti-hyperalgesic action when assessed in chemical, but not thermal, models of nociception in mice and rats. Its analgesic action seems to be unrelated to release or activation of the opioid system.
Psammosilene tunicoides W.C.Wu et C Y.Wu root extract
Ethnopharmacological relevance: The root of Psammosilene tunicoides (W. C. Wu et C. Y. Wu) is a well-known medicinal herb for the treatment of pain, hemostasia and rheumatoid arthritis among Chinese people.
Aim of the study: The present study aimed to investigate the antinociceptive activity and mechanism of β-carboline alkaloids 1–4 which were extracted from the roots of P. tunicoides.
Materials and methods: The analgesic effects were evaluated using peripheral and central pain mouse models of nociception, including the formalin test and the tail flick test. The levels of glutamic acid (Glu) and nitric oxide (NO) in cerebellar cortexes and spinal cords (L4-6) were determined. The anti-inflammatory of all compounds were then assessed on RAW264.7 cells.
Results:Our results showed that compounds 1–4 had significant analgesic effects on both phases of formalin test of mice. Furthermore, all compounds showed suppressive effects on Glu in the brain and NO levels in the brain cortex and the spinal cord. Except for compound 1, the others could extend the pain threshold of hot water tail-flick in mice. In addition, compounds 2 and 3 (60 μmol/kg) could decrease GABAAα1 protein levels in spinal cord. All compounds exhibited anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced NO production in RAW264.7 cells with half-maximal inhibitory concentration (IC50) 1.1–34.9 μM.
Conclusion:β-carboline alkaloids from the roots of P. tunicoides had significant analgesic activity by both central and peripheral mechanisms. Our findings suggested that regulating the release of NO or Glu or GABAα1 are some of the mechanisms of analgesic activity of β-carboline alkaloids.
Psychotria sarmentosa Blume (Family: Rubiaceae)
An unboiled water extract (UBE) of stems and leaves of Psychotria sarmentosa Blume (Family: Rubiaceae) is drunk by some men in Sri Lanka after being physically assaulted, indicating that it may have potent analgesic and/or anti-inflammatory activity. However, these activities are not described in either the Sri Lankan Ayurveda Pharmacopoeia or the Deshiya Chikithsa system of medicine practised in Sri Lanka. The aim of this study was to investigate whether an UBE of these parts of P. sarmentosa has such activities. Different doses of the U B E (7.5, 15.0 and 22.5 ml/kg) or vehicle were administered orally to rats. 1 and 3 h later, the analgesic potential was determined using hot plate and tail flick tests. In another set of rats, the highest dose of U B E was orally administered, and paw oedema induced with 1% car- rageenan. anti-inflammatory activity (up to 4 h) and antihy- peralgesic activity (at 1 h) were determined (by the hot plate technique).
All the doses of U B E were well tolerated and the highest had potent analgesic activity (in both tests, in terms of reaction time and % maximum possible effect) and anti- hyperalgesic activity (measured 1 h post-treatment). The UBE had no anti-inflarmnatory activity. Its analgesic activity was comparable to that of indomethacin and was not blocked by naloxone, (opioid receptor blocker), metochlopramide (dopamine receptor blocker) or atropine (cholinergic receptor blocker).
We conclude that the antinociceptive activity of the U B E was mediated both spinally and supraspinally, and the antihyperalgesic activity spinally. Both actions may have been mediated through a paracetamol type of action
Pterocephalus hookeri
Aim of the study: This study evaluates the anti-inflammatory and analgesic activities of the ethanol and aqueous extracts of a Tibetan herb Pterocephalus hookeri (C.B. Clarke) Höeck to provide experimental evidence for its traditional use such as cold, flu and rheumatoid arthritis.
Materials and methods: Investigations on the analgesic effects of P. hookeri (C.B. Clarke) Höeck were carried out, including hot-plate test and acetic acid-induced writhing. The anti-inflammatory activities were observed by utilizing the following models: carrageenin-induced edema of the hind paw of rats, cotton pellet-induced granuloma formation in rats, acetic acid-induced permeability, and xylene-induced ear edema in mice. The effects of the administration of indomethacin were also studied.
Results: It has been shown that the ethanol and aqueous extracts significantly increased the hot-plate pain threshold and reduced acetic acid-induced writhing response in mice. The ethanol and aqueous extracts remarkably inhibited the increase in vascular permeability induced by acetic acid and ear edema induced by xylene. The ethanol extract also significantly decreased the carrageenin-induced rat paw edema perimeter and inhibited the increase of granuloma weight.
Conclusion: The results show that the ethanol and aqueous extracts have both central and peripheral analgesic activities and as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.
Ethnopharmacological relevance: Pterocephalus hookeri (C.B. Clarke) Höeck, one of the most popular Tibetan herbs, has been widely applied in Tibetan medicine prescriptions. Chemical investigations have led to the isolation of many bis-iridoids. However, the pharmacological activities of bis-iridoid constituents of this plant have never been reported before.
Aim of the study: This study evaluated the anti-inflammatory and analgesic activities of afraction of bis-iridoid constituents of P. hookeri (BCPH) in order to provide experimental evidence for its traditional use, such as for cold, flu, and rheumatoid arthritis.
Materials and methods: The analgesic effects of BCPH were investigated using the hot-plate test and acetic acid-induced writhing test. The anti-inflammatory activities were observed using the following models: carrageenin-induced edema of the hind paw of rats and xylene-induced ear edema in mice. The effects of dexamethasone administration were also studied.
Results: BCPH significantly increased the hot-platepain threshold and reduced acetic acid-induced writhing response in mice. Moreover, BCPH remarkably inhibited xylene-induced ear edema and reduced the carrageenin-induced rat paw edema perimeter.
Conclusion: The results reveal that BCPH has central, peripheral analgesic activities as well as anti-inflammatory effects, supporting the traditional application of this herb in treating various diseases associated with inflammation and pain.
Context: Pterocephalus hookeri (C. B. Clarke) Hock., a traditional Tibetan herbal medicine rich in glycosides, has been used to treat several diseases including rheumatoid arthritis.
Objective: To evaluate the anti-arthritic activity of total glycosides from P. hookeri, and its possible mechanisms of action.
Materials and methods: Anti-arthritic activity of total glycosides from P. hookeri (oral administration for 30 days at 14–56 mg/kg) was evaluated using paw swelling, arthritis scores and histopathological measurement in adjuvant-induced arthritis (AA) Sprague-Dawley rats. The NF-κB p65 expression in synovial tissues, and serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels was measured in AA rats, respectively. Further assessment of anti-inflammatory and analgesic activities of these glycosides were carried out using inflammation and hyperalgesia models induced by xylene, carrageenan, agar and acetic acid, respectively.
Results: Total glycosides (56 mg/kg) decreased the paw swelling (38.0%, p < 0.01), arthritis scores (25.3%, p < 0.01) and synovial inflammation in AA rats. The glycosides significantly (p < 0.05–0.01) attenuated the inflammation induced by xylene, carrageenan, acetic acid and agar, increased the pain threshold in acetic acid-induced writhing in mice and mechanical stimuli-induced hyperalgia in AA rats. The glycosides (14, 28, 56 mg/kg) also suppressed the NF-κB p65 expression (33.1–78.2%, p < 0.05–0.01), reduced MDA (21.3–35.9%, p < 0.01) and NO (20.3–32.4%, p < 0.05–0.01) levels, respectively, enhanced the SOD activity (7.8%, p < 0.05) at 56 mg/kg in AA rats.
Conclusion: Our findings confirmed the anti-arthritic property of the total glycosides from P. hookeri, which may be attributed to its inhibition on NF-κB signalling and oxidative stress.
Punica granatum (Flower)
analgesic and anti-inflammatory activities of Flower extracts of Punica granatum Linn. (Punicaceae)
Punica granatum has been used for centuries to confer health benefits in a number of inflammatory diseases. Based on its usage in Ayurvedic and Unani medicine, dietary supplements containing pomegranate extract are becoming popular for the treatment and prevention of arthritis and other inflammatory diseases. Pet-ether, dichloromethane and methanol fractions of flower part were chosen for pharmacological screening and analgesic and anti-inflammatory activities in animal model.
The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model. The analgesic effect was measured in mice using the acetic acid-induced writhing test. In the acetic acid-induced writhing test in mice, pet-ether, dichloromethane and methanol fractions at 200 mg/kg doses level showed 75.77% (p
Pycnogenol (maritime pine bark)
natural anti-inflammatory agents for pain relief
The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements.
Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use.
Qianghuo Shengshi
Qianghuo Shengshi decoction exerts anti-inflammatory and analgesic via MAPKs/CREB signaling pathway
Ethnopharmacological relevance: Traditional Chinese medicine Qianghuo Shengshi decoction (QSD) is widely used in the treatment of nervous headache, rheumatoid arthritis, sciatica, allergic purpura, and other clinical diseases in China. However, the underlying mechanisms of its anti-inflammatory and analgesic effects has not been elucidated.
Aim of the study: The aim of this study was to confirm the anti-inflammatory and analgesic effects and the underlying mechanism of QSD in vivo. In addition, this study was also to isolate and analyze the main active components of QSD by high performance liquid chromatography (HPLC).
Materials and methods: In this study, the acetic acid writhing test, hot plate test and ear swelling test and formalin test were carried out to explore the anti-inflammatory and analgesic effects of QSD. The doses were set to 7.8 g/kg, 15.6 g/kg and 31.2 g/kg body weight. Western blot was utilized to study further possible mechanisms of QSD. Moreover, the HPLC method was used to isolate and identify the components in the extraction of QSD.
Results: Twelve characteristic peaks were recognized in the HPLC spectrum, which all were the known compounds. The QSD exhibited dose-dependent effects in anti-inflammatory and analgesic aspects. Compared with model group, the writhing times of in groups of different doses of QSD (15.6 g/kg and 31.2 g/kg (oral administration = p.o.)) were reduced by 33.0% and 45.8% and indicated the QSD showed significant (p < 0.05) peripheral analgesic effect. QSD ((31.2 g/kg), p.o.) showed significant(p < 0.05) analgesic effect in the hot plate test. inhibition rates of QSD ((15.6 g/kg and 31.2 g/kg), p.o.) in ear swelling test induced by p-xylene were 27.5% and 54.6% and demonstrated the significant (p < 0.05) anti-inflammatory activity. QSD ((31.2 g/kg), p.o.) significantly (p < 0.05) reduced times of paw licking in formalin test, and its inhibition rates were 34.3% and 28.0% in Phase I and Phase Ⅱ response, respectively. Western blot results showed that QSD inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) protein and cAMP response element-binding protein (CREB).
Conclusion: These results of this study undoubtedly confirmed that QSD expressed obvious analgesic and anti-inflammatory activities. anti-inflammatory and analgesic effects of QSD may be achieved by regulating the MAPKs protein and further regulating the expression of CREB. In all, QSD may play an anti-inflammatory and analgesic role through a variety of active ingredients.
Resveratrol
natural anti-inflammatory agents for pain relief
The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements.
Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use.
Ricinus communis L. seed extract
antinociceptive activity of Ricinus communis L. leaves
Objective: To evaluate the antinociceptive activity of the methanol extract of Ricinus communis leaves (MRCL).
Methods: Antinociceptive activity was evaluated using acetic acid induced writhing test, formalin induced paw licking and tail immersion method in mice at doses of 100, 125 and 150 mg/kg bw.
Results: The results indicated that MRCL exhibited considerable antinociceptive activity against three classical models of pain in mice. Preliminary phytochemical analysis suggested the presence of saponin, steroids and alkaloids.
Conclusions: It can be concluded that MRCL possesses antinociceptive potential that may be due to saponin, steroids and alkaloids in it.
Rosa damascena (Rosaceae)
Extracts obtained from the petals of Rosa damascena (Rosaceae) are used in Iranian folk medicine as remedies for the treatment of some inflammatory diseases. In this study the hydroalcoholic extract and essential oil of the plant were investigated for its possible anti-inflammatory and analgesic activities. The extract was administered at the doses (p.o.) of 250, 500 and 1000 mg/kg and the doses of essential oil were 100, 200 and 400 μL/kg. The acetic acid-induced writhing response, formalin-induced paw licking time in the early and late phases and light tail flick test were used in mice to assess analgesic activity. For evaluation of anti-inflammatory effect carrageenan-induced paw edema served as a valid animal model in rats.
The extract significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and also showed potent analgesic effect in both phases of formalin test but not in light tail flick test. In addition, the higher dose of the extract significantly (P < 0.05) reduced carrageenan-induced paw edema. essential oil of the plant at all administered doses failed to show any analgesic or anti-inflammatory effect in above mentioned tests.
These results provide support for the use of hydroalcoholic extract of Rosa damascena in relieving inflammatory pain, and insight into the development of new agents for treating inflammatory diseases.
rosmarinic acid
Background: Rosemary, Rosmarinus (R.) officinalis L. is a well-known plant with several useful properties such as analgesic, anti-inflammatory and anti-neurodegenerative. It has been used in folk medicine to alleviate rheumatic pain, stomachache and dysmenorrhea. Rosemary has several constituents such as rosmarinic acid which can be responsible for therapeutic properties been noted with rosemary. The aim of this study was to investigate the potential anti-inflammatory effects of R. officinalis and rosmarinic acid in a rat model of sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain to verify usage of rosemary in folk medicine.
Methods: Rats underwent CCI, were treated with either normal saline, ethanolic extract of aerial parts of R. officinalis (400 mg/kg, i.p.) or rosmarinic acid (40 mg/kg, i.p.) from the day of surgery (day 0) for 14 days. The anti-inflammatory effects of R. officinalis extract and rosmarinic acid were evaluated by assessing the levels of some spinal inflammatory markers including cyclooxygenase-2 (COX2), prostaglandin E2 (PGE-2), interleukin 1 beta (IL-1β), matrix metallopeptidase 2 (MMP2) through western blotting and nitric oxide (NO) production via Griess reaction on days 7 and 14 post-surgery.
Results:CCI rats exhibited a marked expression in the levels of inflammatory markers (COX2, PGE-2, IL-1β, MMP2 and NO) on both days 7 (p < 0.001) and 14 (p < 0.001). Rosmarinic acid and ethanolic extract of R. officinalis were able to decrease amounts of mentioned inflammatory markers on both days 7 (p < 0.001) and 14 (p < 0.001).
Conclusion: Our data support the traditional use of R. officinalis as an effective remedy for pain relief and inflammatory disorders. It also suggests that the ethanolic extract of R. officinalis and rosmarinic acid through modulating neuro-inflammation might be potential candidates in treating neuropathic pain and different neurological disorders associated with inflammation.
Ethnopharmacological relevance: According to traditional medicine, rosemary (Rosmarinus officinalis) has been used in many ailments such as dysmenorrhea, rheumatic pain and stomachache.
Aim of the study: This work was carried out to evaluate putative anti-allodynic and anti-hyperalgesic effects of Rosmarinus officinalis alcoholic extract and some spinal cord molecular changes on a neuropathic pain model in rats.
Materials and methods: Peripheral neuropathy was induced by chronic constriction injury (CCI) of sciatic nerve. Rats were treated daily with alcoholic extract of aerial parts of R. officinalis (100, 200, and 400 mg/kg, i.p.), from the day of surgery (day 0) for 14 days. Mechanical allodynia, cold allodynia and heat hyperalgesia were measured on days 0, 3, 5, 7, 10 and 14. Investigations into mechanisms involved measurement of apoptotic factors (bcl-2-like protein (Bax)), cleaved caspases 3 and 9, anti-apoptotic mediator, Bcl2, inflammatory mediators including tumor necrosis factor alpha (TNF-α), inducible isoform of nitric oxide synthase (iNOS), toll like receptor 4 (TLR4), microglial activation marker, ionized calcium-binding adapter molecule 1 (Iba-1) and astroglia activation marker, glial fibrillary acidic protein (GFAP) were measured via western blot on days 7 and 14.
Results: CCI rats exhibited a marked mechanical allodynia, cold allodynia, and thermal hyperalgesia on days 3, 5, 7, 10, and 14 post-CCI. All three doses of rosemary alcoholic extract were able to attenuate neuropathic behavioral changes as compared with CCI animals that received vehicle. In the vehicle-treated CCI group, a significant increase in levels of Bax, cleaved caspases 3 and 9, Iba1, TNF-α, iNOS and TLR4 levels was detected on both days 7 and 14. Rosemary extract, 400 mg/kg significantly decreased the amounts of mentioned apoptotic, inflammatory and glial markers as compared with vehicle-treated CCI animals.
Conclusion: Anti-inflammatory and anti-apoptotic processes might contribute to the anti-allodynic and anti-hyperalgesic effects of rosemary following nerve injury. Our findings support the ethnopharmacological use of rosemary as a potential candidate in treating neuropathic pain and different neurological disorders that associate with the activation of apoptosis and inflammatory pathways.
Rumex crispus (aerial)
anti-inflammatory, analgesic and hepatoprotective effect of Semen of Rumex crispus
Roots of Rumex crispus (Rc) (Polygonaceae) has been used as therapeutic agents of acute and chronic cutaneous diseases, cathartics, fever and jaundice in folk medicines. Recently, seeds of Rc has known as a digestive, an anticancer agent and a remedy of acute hepatitis, among many traditional folk medicines. So far it isn’t reported about pharmacological effects of Rumecis Semen.
The present study describes the preliminary evaluations of biological activities, anti-inflammatory activity (AA, Carrageenan) analgesic activity (writhing test), and hepatoprotective activities (), of its methanol extract, ethyl acetate fraction and butanol fraction. Among them butanol fraction showed the highest activity in analgesic acivity.
Salvia miltiorrhiza Bge.root extract
The pharmacological effects of Salvia species on the central nervous system
Salvia is an important genus consisting of about 900 species in the family Lamiaceae. Some species of Salvia have been cultivated world wide for use in folk medicine and for culinary purposes. The dried root of Salvia miltiorrhiza, for example, has been used extensively for the treatment of coronary and cerebrovascular disease, sleep disorders, hepatitis, hepatocirrhosis, chronic renal failure, dysmenorrhea, amenorrhea, carbuncles and ulcers. S. officinalis, S. leriifolia, S. haematodes, S. triloba and S. divinorum are other species with important pharmacological effects. In this review, the pharmacological effects of Salvia species on the central nervous system will be reviewed.
These include sedative and hypnotic, hallucinogenic, skeletal muscle relaxant, analgesic, memory enhancing, anticonvulsant, neuroprotective and antiparkinsonian activity, as well as the inhibition of ethanol and morphine withdrawal syndrome.
arthritis is a common condition that causes pain and inflammation in a joint. Previously, we reported that the mixture extract (ME) from Agrimonia pilosa Ledeb. (AP) and Salvia miltiorrhiza Bunge (SM) could ameliorate gout arthritis. In the present study, we aimed to investigate the potential anti-inflammatory and antinociceptive effects of ME and characterize the mechanism. We compared the anti-inflammatory and antinociceptive effects of a positive control, Perna canaliculus powder (PC).
The results showed that one-off and one-week treatment of ME reduced the pain threshold in a dose-dependent manner (from 10 to 100 mg/kg) in the mono-iodoacetate (MIA)-induced osteoarthritis (OA) model. ME also reduced the plasma TNF-α, IL-6, and CRP levels. In LPS-stimulated RAW 264.7 cells, ME inhibited the release of NO, PGE2, LTB4, and IL-6, increased the phosphorylation of PPAR-γ protein, and downregulated TNF-α and MAPKs proteins expression in a concentration-dependent (from 1 to 100 µg/mL) manner.
Furthermore, ME ameliorated the progression of ear edema in mice. In most of the experiments, ME-induced effects were almost equal to, or were higher than, PC-induced effects. conclusions: The data presented here suggest that ME shows anti-inflammatory and antinociceptive activities, indicating ME may be a potential therapeutic for arthritis treatment.
medicinal plants from traditional chinese medicine are used increasingly worldwide for their benefits to health and quality of life for the relevant clinical symptoms related to pain. Among them, Salvia miltiorrhiza Bunge is traditionally used in asian countries as antioxidant, anticancer, anti-inflammatory and analgesic agent. In this context, several evidences support the hypothesis that some tanshinones, in particular cryptotanshinone (CRY), extracted from the roots (Danshen) of this plant exhibit analgesic actions. However, it is surprisingly noted that no pharmacological studies have been carried out to explore the possible analgesic action of this compound in terms of modulation of peripheral and/or central pain.
Therefore, in the present study, by using peripheral and central pain models of nociception, such as tail flick and hot plate test, the analgesic effect of CRY in mice was evaluated. Successively, by the aim of a computational approach, we have evaluated the interaction mode of this diterpenoid on opioid and cannabinoid system. Finally, CRY was dosed in mice serum by an HPLC method validated according to European medicines Agency guidelines validation rules.
Here, we report that CRY displayed anti-nociceptive activity on both hot plate and tail flick test, with a prominent long-lasting peripheral analgesic effect. These evidences were indirectly confirmed after the daily administration of the tanshinone for 7 and 14 days. In addition, the analgesic effect of CRY was reverted by naloxone and cannabinoid antagonists and amplified by arginine administration. These findings were finally supported by HPLC and docking studies, that revealed a noteworthy presence of CRY on mice serum 1 h after its intraperitoneal administration and a possible interaction of tested compound on μ and k receptors.
Taken together, these results provide a new line of evidences showing that CRY can produce analgesia against various phenotypes of nociception with a mechanism that seems to be related to an agonistic activity on opioid system.
Sargassum ilicifolium brown seaweed
Background: The methanolic extract of Sargassum ilicifolium (Pheophyceae) was used to evaluate its analgesic and anti-inflammatory activity in the present study.
Materials and Methods: Analgesic activity was tested using Acetic acid writhing method and Eddy hot plate method in Male albino mice and Wister rats respectively at a dose level of 1, 10, 50, 100mg/kg p.o. At the same dose, its anti-inflammatory activity was also tested using Carrageenan induced rat paw edema method result Acetic acid writhing test and Eddy’s hot plate episodes were significantly and dose dependently reduced. Carrageenan (a standard inflammatory agent) induced paw edema in rats was significantly reduced after intraperitonal administration of methanolic extract.
Results: Showed dose dependant significant activity in comparison with standard and control.
Conclusion: Methanolic extracts of the brown seaweeds Sargassum ilicifolium have potent analgesic and anti-inflammatory activity at moderate doses.
Solanum torvum
Solanum torvum is used in Cameroonian traditional medicine for the management of pain and inflammation. The present work assesses the pain-killing and anti-inflammatory properties of the aqueous extracts of Solanum torvum leaves. Acetic acid- and pressure- induced pains were reduced by this extract while carrageenan-induced inflammation was inhibited at various doses of the extract. The extract therefore has both analgesic and anti-inflammatory properties.
Solanum tuberosum L.) peel extract
Evaluation Of analgesic potential Of Solanum Trilobatum roots
In the present work, the antinociceptive action was assayed in several experimental models in mice: writhing, formalin and hot plate tests. The crude alkaloid fraction (25, 50, 100 mg/kg) and in a dose-dependent manner significantly reduced the nociception by acetic acid intTaperitoneal injection (P<0.00 I). In the formalin test, the extract (50 and 100 mg/kg) also significantly reduced the painful stimulus in both phases of the test (P<0.001). treatment with the extract (25, 50, 100 mg/kg) when given i.p. or pentazocine (5 mg/kg, s.c.) produced a significant increase of the reaction time in hot plate test.
These result showed that the alkaloid extract of Solanum trilobatum contains active analgesic principles acting both centrally and peripherally.
The utilization of natural resources, one of which is plants, has been researched as an alternative to synthetic drugs because of their natural content. Potato (Solanum tuberosum L.) peels, the parts of potatoes that are often cut off and discarded, have been reported to have some phenolic compounds and flavonoids in their composition. The extract of potato peels was investigated for its analgesic, anti-inflammatory, and anti-biofilm-forming properties. A hot plate test was conducted to assess the analgesic activity in treatment doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg with paracetamol as the reference drug and distilled water as the negative control, while carrageenan-induced paw edema was used to assess anti-inflammatory activity in treatment doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg with diclofenac as the reference drug and distilled water as the negative control. Anti-biofilm-forming activity was tested by using the crystal violet assay.
The results showed that, compared with the negative control, treatment doses of 100 mg/kg and 200 mg/kg significantly (p < 0.05) reduced pain stimuli, whereas a treatment dose of 100 mg/kg, 200 mg/kg, and 400 mg/kg significantly (p < 0.05) reduced the edema volume increment. However, compared with the positive control, paracetamol and diclofenac were associated with the least pain stimulus and the least edema volume increment, respectively. Potato peel extract against S. mutans biofilm formation demonstrated effectiveness (p < 0.05).
Based on these data, it can be concluded that potato peel extract has analgesic, anti-inflammatory, and anti-biofilm-forming activities, as demonstrated in this study.
Spatholobus.suberectus Dunn extract
The dried vine stems of Spatholobus suberectus are commonly used in traditional Chinese medicine for treating gynecological and cardiovascular diseases. In this study, five new compounds named spasuberol A (2), homovanillyl-4-oxo-nonanoate (5), spasuberol C (6), spasuberoside A (14), and spasuberoside B (15), together with ten known compounds (1, 3, 4, 7–13), were isolated from the dried vine stems of S. suberectus. Their chemical structures were analyzed using spectroscopic assays. This is the first study interpreting the detailed structural information of 4.
The anti-inflammatory activity of these compounds was evaluated by reducing nitric oxide overproduction in RAW264.7 macrophages stimulated by lipopolysaccharide. Compounds 1 and 8–10 showed strong inhibitory activity with half maximal inhibitory concentration (IC50) values of 5.69, 16.34, 16.87, and 6.78 μM, respectively, exhibiting higher activity than the positive drug l-N6-(1-iminoethyl)-lysine (l-NIL) with an IC50 value of 19.08 μM. The IC50 values of inhibitory activity of compounds 2 and 4–6 were 46.26, 40.05, 45.87, and 28.29 μM respectively, which were lower than l-NIL, but better than that of positive drug indomethacin with an IC50 value of 55.44 μM.
Quantitative real-time polymerase chain reaction analysis revealed that assayed compounds with good anti-inflammatory activity, such as 1, 6, 9, and 10 at different concentrations, can reduce the messenger RNA (mRNA) expression of some pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). The anti-inflammatory activity and the possible mechanism of the compounds mentioned in this paper were studied preliminarily.
Spilanthes acmella Linn.var.oleracea Clarke extract
To evaluate the antiinflammatory and analgesic activities of the aqueous extract of Spilanthes acmella (SPA) in experimental animal models.
SPA was evaluated for antiinflammatory action by carrageenan-induced rat paw edema. The analgesic activity was tested by acetic acid-induced writhing response in albino mice and tail flick method in albino rats.
The aqueous extract of SPA in doses of 100, 200 and 400 mg/kg showed 52.6, 54.4 and 56.1% inhibition of paw edema respectively at the end of three hours and the percentage of protection from writhing was 46.9, 51.0 and 65.6 respectively. In the tail flick model, the aqueous extract of SPA in the above doses increased the pain threshold significantly after 30 min, 1, 2 and 4 h of administration. SPA showed dose-dependent action in all the experimental models.
The present study indicates that SPA has significant antiinflammatory and analgesic properties.
Stauntonia chinensis DC. extract
Triterpenoid saponins from Stauntonia chinensis (TSS) are potential therapeutic agents because of its analgesic properties. However, the underlying mechanisms of the anti-nociceptive activity of TSS are largely unclear, especially in CNS. The present study confirmed the analgesic effect of TSS using four models of acute pain based on thermal or chemical stimuli. TSS treatment specifically impaired the threshold of thermal- and chemical-stimulated acute pain. Naloxone did not block the anti-nociceptive effects of TSS, which showed no participation of the opioid system. We investigated the electrical signal in cultured cortical neurons to explore whether TSS treatment directly affected synaptic transmission. TSS treatment selectively increased spontaneous inhibitory synaptic release and GABA induced charge transfer in mouse cortical neurons.
The effects of TSS were maintained for at least 8 h in cultured neurons and in injected mice. Taken together, our results suggest that the analgesic role of TSS in cortex occurs via a particular increase in the inhibitory synaptic response at resting state, which supports TSS as a potential candidate for inflammatory pain relief.
The aim of this investigation was to study the anti-nociceptive and anti-inflammatory activities of Stauntonia chinensis (S. chinensis) and the possible action mechanisms of effective fractions. The anti-nociceptive and antiinflammatory activities of S. chinensis extracts, including the 60% EtOH extract (YMG), the n-BuOH extract (YMGB) and the aqueous residue (YMGW) of YMG, and the fractions from YMGB (YMGB1~YMGB7) were investigated by using the mouse acetic acid-induced writhing test and the rat formalin test.
The effect of these extracts on the PGE2 production was tested as well. In the mouse acetic acid-induced writhing test and the rat formalin test, YMGW and YMGB displayed anti-nociceptive and anti-inflammatory activities, suggesting that they were the active ingredients of YMG. Among the fractions isolated from YMGB, YMGB1, YMGB3, YMGB4 and YMGB6 were the main active ingredients producing anti-nociceptive activity and YMGB3, YMGB5, YMGB6 and YMGB7 were the main active ingredients producing anti-inflammatory activity. Additionally, YMGW, YMGB and its separations reduced the production of PGE2, which might be the mechanism of them producing anti-inflammatory activity.
These results demonstrated the active ingredients of S. chinensis producing anti-nociceptive and anti-inflammatory activities, which is valuable to validate the substance basis of S. chinensis’s pharmacological actions.
Bidesmoside triterpenoid glycosides from Stauntonia chinensis and relationship to anti-inflammation
Ten triterpenoid glycosides, yemuoside YM26–35 (1–9 and 12), were isolated from a traditional Chinese medicine known as “Ye Mu Gua” (Stauntonia chinensis DC.) along with two known ones, kalopanax saponin C (10) and sieboldianoside A (11). Their structures, as elucidated by spectroscopic analyses and chemical methods, were either penta-saccharidic or hexa-saccharidic bidesmoside triterpenoid glycosides. To help explain the clinical applications of “Ye Mu Gua” for its anti-inflammatory effects, the inhibitory activity on the release of inflammatory mediators (nitric oxide, TNF-α and IL-6) of 1–12 and the related aglycone, hederagenin (13), was evaluated in vitro. It was found that compound 13, but not 1–12, exhibited significant inhibitory activity.
The abundant triterpenoid glycosides in “Ye Mu Gua” might therefore be transformed into their respective aglycones, and thus inhibit the release of inflammatory factors in vivo. This could then account for the clinical value of “Ye Mu Gua” as regards anti-inflammatory effects. This proposed explanation of how “Ye Mu Gua” may have an effect is similar to the concept of prodrugs for chemical drugs which could be extended to some traditional medicines. That is, the major components might be biologically active not directly, but via biochemical transformation in vivo. Hence, we propose a “traditional medicine’s prodrug characteristic” concept.
Stephania japonica (Linn.) leaf extract
The present study was conducted to evaluate the possible phytochemicals present, antioxidant activity and analgesic potential of ethanolic extract of leaves of Stephania japonica (Linn.). For investigating the antioxidant activity, four complementary test systems, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, reducing power assay, Fe++ ion chelating ability and total phenolic content were used. analgesic activity of the extract was evaluated using acetic acid-induced writhing model of pain in mice. In DPPH free radical scavenging test, IC 50 value for ethanolic crude extract was found moderate (18.57 ± 0.079 μg/ml) while compared to the IC50 values of the reference standards ascorbic acid and BHA (1.93 ± 0.027 and 4.10 ± 0.035 μg/ml), respectively.
In reducing power assay, the maximum absorbance for ethanolic crude extract was found to be 2.013 ± 0.024 at 100 μg/ml, compared to 2.811 ± 0.013 and 2.031 ± 0.019 for standard ascorbic acid and butylated hydroxyanisole (BHA), respectively. The IC 50 value of the extract as % Fe ++ ion chelating ability was determined as 18.68 ± 0.029, where ethylenediaminetetraacetic acid (EDTA) showed 8.87 ± 0.035.
The total phenolic amount was also calculated as moderate in ethanolic crude extract (237.71 ± 0.57 mg/g of gallic acid equivalent). At the dose of 500 mg/kg body weight, the extract showed significant analgesic potential in acetic acid induced writhing in mice, showing 41.47% inhibition (P < 0.001) comparable to that produced by diclofenac Na (45.02%) used as standard drug. These results show that ethanolic extract of leaves of S. japonica (Linn.) has moderate antioxidant and potent analgesic activity.
These activities increase with the increase of concentrations. The potency of the extract may be due to the presence of phytochemicals like tannins, flavonoids, phenolics etc.
Strychnos nux-vomica L. (Loganiaceae)
To further understand the purpose of the traditional processing method of the seeds of Strychnos nux-vomica L. (Loganiaceae) as well as analgesic and anti-inflammatory activities of brucine and brucine N-oxide extracted from this medicinal plant from ScienceDirect’s AI-generated Topic Pages” medicinal plant, various pain and inflammatory models were employed in the present study to investigate their pharmacological profiles. Both brucine and brucine N-oxide revealed significant protective effects against thermic and chemical stimuli in hot-plate test and writhing test. However, on different phases they exerted analgesic activities in formalin test.
Brucine N-oxide showed stronger inhibitory effect than brucine in carrageenan-induced rat paw edema, both of them significantly inhibited the release of prostaglandin E2 in inflammatory tissue, reduced acetic acid-induced vascular permeability and the content of 6-keto-PGF1a in Freund’s complete adjuvant (FCA) induced arthritis rat’s blood plasma. In addition, brucine and brucine N-oxide were shown to reduce the content of 5-hydroxytryptamine (5-HT) in FCA-induced arthritis rat’s blood plasma, while increase the content of 5-hydroxytryindole-3-acetic acid (5-HIAA) accordingly.
These results suggest that central and peripheral mechanism are involved in the pain modulation and anti-inflammation effects of brucine and brucine N-oxide, biochemical mechanisms of brucine and brucine N-oxide are different even though they are similar in chemical structure.
Ethnopharmacological relevance: Strychnos nux-vomica L. (Loganiaceae) is grown extensively in southern Asian countries. The dried seed of this plant, nux vomica, has been clinically used in Chinese folk medicine for improving blood circulation, relieving rheumatic pain, reducing swelling and treating cancer.
Aim of the study: This study was carried out to investigate the effect of removing most strychnine from the total alkaloid fraction (TAF) extracted from nux vomica on analgesic and anti-inflammatory activity and pharmacokinetics after transdermal administration.
Materials and methods: Most strychnine was removed from TAF and the resulted modified total alkaloid fraction (MTAF) was obtained. The contents of strychnine and brucine in TAF and MTAF were determined. Then the analgesic and anti-inflammatory activity of TAF, MTAF, brucine and strychnine dissolved in hydrogel was compared after transdermal administration. Furthermore, in vitro and in vivo transdermal absorption profiles of brucine after administration of TAF, MTAF and brucine dissolved in hydrogel were also compared.
results
Results: In contrast to TAF, most strychnine was removed from MTAF and the ratio of brucine to strychnine was adjusted from 1:1.8 to 2.7:1. MTAF showed significant analgesic activity in all the chemical-, thermal- and physical– induced nociception models, which indicated the presence of both centrally and peripherally mediated activities. MTAF also showed significant anti-inflammatory activity against xylene-induced ear edema. But TAF and strychnine demonstrated little activity in all those pharmacological tests. Brucine showed to be effective in acetic acid-induced writhing and xylene-induced ear edema test. Brucine in MTAF was absorbed more completely than it alone at the same dosage of brucine after transdermal administration.
Conclusion: The results from the present study appeared to support the viewpoint that most strychnine should be removed from TAF to improve analgesic and anti-inflammatory activity. The relatively higher pharmacological activity of MTAF compared to brucine alone is partly due to the enhanced transdermal absorption of brucine.
The strychnine tree (Strychnos nux–vomica L.) (S. nux–vomica) belonging to family Loganiaceae has been a very promising medication for certain disorders. Different chromatographic methods were used to isolate the phenolic compounds from the aqueous methanolic extract of the S. nux–vomica leaves. Their identification was achieved through spectroscopic techniques. Cytotoxicity, analgesic, antipyretic and anti-inflammatory activities of S. nux–vomica leaves extract were evaluated. Five phenolic compounds were isolated and identified; Kaempferol-7 glucoside 1, 7-Hydroxy coumarin 2, Quercetin-3-rhamnoside 3, Kaempferol 3-rutinoside 4, and Rutin 5.
Furthermore, the cytotoxic activity of the extract was evaluated against different cancer cell lines. The extract showed potential cytotoxic activity against human epidermoid larynx carcinoma cells (Hep-2) and against breast carcinoma cell line (MCF-7). Colon carcinoma cells (HCT) were the least one affected by the extract. In addition, the extract exhibited promising analgesic, antipyretic as well as anti-inflammatory activities. It is concluded that, leaves extract of S. nux vomica possess potent cytotoxic, analgesic, antipyretic and anti-inflammatory activities. These activities could be due to the presence of phenolic compounds revealed by our phytochemical investigations.
analgesic and anticonvulsant effects of extracts from the leaves of Strychnos nux vomica linn
Strychnos nux vomica belongs to the family Loganiaceae is a fleshy herbaceous plant used in the Indian traditional medicine as nervine stomachic, tonic, aphrodiasic, spinal stimulant, also respiratory and cardiac stimulant. In excessive doses, it is a virulent poison producing titanic convulsions 1. In the present work, the analgesic effects of methylene chloride/methanol (I:I) (CH2Cl2/ CH3OH) extract and its hexane, methylene chloride (CH2Cl2), ethyl acetate, n-butanol fractions and aqueous residue has been evaluated using acetic acid, formalin and pressure test. The anticonvulsant effects of the CH 2Cl2/CH3OH extract were also investigated on seizures induced by pentylene tetrazole (PTZ 70 mg/kg), strychnine sulphate (STN 2.5 mg/kg) an thiosemicarbazide (TSC 50 mg/kg)CH2Cl 2/CH3OH extract and its fractions, administered orally at the doses of 150 and 300mg/kg, exhibited protective effect of at least 30% on the pain induced by acetic acid.
The CH2Cl2 fraction at 300 mg/kg showed a maximal effect of 78.49%. The CH2Cl 2/CH3OH extract and its CH2Cl2 fraction at the doses of 150 and 300 mg/kg significantly reduced the first phase of pain induced by formalin while the second phase was completely inhibited. The CH2Cl2 fraction produced more than 45% reduction in the sensitivity to pain induced by pressure. The CH2Cl 2/CH3OH extract of Strychnos nux vomica significantly increased the latency period in seizures induced by PTZ and significantly reduced the duration of seizures induced by the three convulsant agents. The extract protected 20% of animals against death in seizures induced by TSC and STN . These results suggest a peripheral and central analgesic activities as well as an anticonvulsant effect of the leaves of Strychnos nux vomica.
We examined the antinociceptive effects of the crude alkaloid fractions (CAF) of nux vomica (the dried seeds of Strychnos nux-vomica L.) and the influences of various processing methods upon their antinociception in three analgesic tests in mice. In the tail-pressure test, the CAF (0.01-1 μg/kg, i.p.) of nux vomica that was unprocessed or treated with sand-, licorice-, oil- or vinegar and sand-processing showed clear antinociception. The CAF (1 μg/kg, i.p.) of vinegar-processed nux vomica showed antinociception, without effects at lower doses of 0.01 and 0.1 μg/kg and those treated with urine- or urine and sand-processing were without effects at doses of 0.01-1 μg/kg. morphine (2 mg/kg, s.c.) showed short-lasting antinociception, without effects at a dose of 1 μg/kg. In the hot-plate test, the CAF (100 μg/kg, i.p.) of nux vomica having undergone sand-processing produced a significant antinociception, without effects at lower doses of 0.01 and 1 μg/kg. The CAF (0.01-100 μg/kg, i.p.) of nux vomica that was unprocessed or treated with oil- or vinegar and sand-processing and morphine (1 and 100 μg/kg, s.c.) were without effects.
In the acetic acid-induced writhing test, the CAF (1 μg/kg, i.p.) of nux vomica that was treated with sand-processing significantly inhibited the writhing behavior, while those of nux vomica that was unprocessed or treated with oil- or vinegar and sand-processing and morphine were without effects at a dose of 1 μg/kg. The present results demonstrate the antinociceptive effects of the CAF of nux vomica and suggest that sand-processing is good for the analgesic potency of nux vomica. It is also suggested that the CAF of nux vomica has distinct antinociceptive potency, even after treatment with licorice-, oil-, vinegar and sand-processing.
Termitomyces albuminosus
Aim of the study: The objectives of this study were to investigate the analgesic and anti-inflammatory effects of the dry matter of culture broth (DMCB) of Termitomyces albuminosus in submerged culture and its crude saponin extract (CSE) and crude polysaccharide extract (CPE).
Materials and methods: The analgesic effects of DMCB, CSE and CPE were evaluated with models of acetic acid-induced writhing response and formalin test in mouse. The anti-inflammatory effects of DMCB, CSE and CPE were evaluated by using models of xylene-induced mouse ear swelling and carrageen-induced mouse paw edema.
Results:The DMCB, CSE and CPE significantly decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. treatment of DMCB (1000 mg/kg), CSE (200 mg/kg) or CPE (200 mg/kg) inhibited the mouse ear swelling by 61.8%, 79.0% and 81.6%, respectively. In the carrageen-induced mouse paw edema test, the group treated with indomethacin showed the strongest inhibition of edema formation by 77.8% in the third hour after carrageenan administration, while DMCB (1000 mg/kg), CSE (200 mg/kg) and CPE (200 mg/kg) showed 48.4%, 55.6% and 40.5%, respectively.
Conclusion: The results suggested that DMCB of Termitomyces albuminosus possessed the analgesic and anti-inflammatory activities. Saponins and polysaccharides were proposed to be the major active constituents of Termitomyces albuminosus in submerged culture.
Tetrahydropalmatine
Chronic pain is categorized as inflammatory and neuropathic, and there are common mechanisms underlying the generation of each pain state. Such pain is difficult to treat and the treatment at present is inadequate. Corydalis yanhusuo is a traditional Chinese medicine with demonstrated analgesic efficacy in humans. The potential antihyperalgesic effect of its active component is L-tetrahydropalmatine (L-THP). L-THP has been used for the treatment of headache and other mild pain. However, little is known about its analgesic effect on chronic pain and its mechanism. Here, we report that L-THP exerts remarkable antihyperalgesic effects on neuropathic and inflammatory pain in animal models. neuropathic hypersensitivity was induced by segmental spinal nerve ligation and inflammatory hypersensitivity was induced by an intraplantar injection of complete Freund’s adjuvant.
To determine the receptor mechanism underlying the antihyperalgesic actions of L-THP, we used SCH23390, an antagonist of a dopamine D1 receptor, in an attempt to block the antihyperalgesic effects of L-THP. We found that L-THP (1-4 mg/kg, i.p.) produced a dose-dependent antihyperalgesic effect in spinal nerve ligation and complete Freund’s adjuvant models. The antihyperalgesic effects of L-THP were abolished by a dopamine D1 receptor antagonist SCH23390 (0.02 mg/kg).
Furthermore, L-THP (4 mg/kg, i.p.) did not influence motor function. These findings suggest that L-THP may ameliorate mechanical hyperalgesia by enhancing dopamine D1 receptor–mediated dopaminergic transmission.
Thuja Orientalis (More Pankh)
This study was conducted for evaluating a natural source to treat inflammation and pain, to avoid the severe side effects of currently used agents for these ailments. Thuja Orientalis (More Pankh) is commonly used for the treatment of pain and inflammatory disorders in traditional medicine. Carrageenan induced inflammatory model, acetic acid induced writhing test and hot plate methods were used to evaluate anti-inflammatory, peripheral and central analgesic properties of aqueous methanolic extract of Thuja Orientalis fruit (To-Cr) in albino rats. Completely randomized design (CRD) was constructed for the study and one way ANOVA was applied to compare means.
The results showed that TO-Cr has significant anti-inflammatory and analgesic properties
analgesic activity of Thuja orientalis leaves
Present study reports analgesic activity of petroleum ether, chloroform, methanolic and aqueous extract of leaves of Thuja orientalis. Hot plate and tail immersion methods were used for evaluation of central analgesic activity and acetic acid induced writhing model was used for evaluation of peripheral analgesic activity. Hot plate acetic acid induced writhing model was used for evaluation of central analgesic activity as well as peripheral analgesic activity.
Results indicate that petroleum ether extract of leaves at 50 mg/kg, i.p. dose produced a significant increase in reaction time (P<0.05) in tail immersion method and increased in response latency period (P<0.05) in hot plate method, against standard drug pentazocin. Aqueous extract of leaves of Thuja orientalis significantly (P<0.05) attenuated the number of writhing when compared to standard drug paracetamol in acetic acid induced writhing model.
Typha angustifolia pollen
Edible medicinal and Non-medicinal plants
100 coloured illustrations in this volume. Referenced up-to-date-information on nutritive and medicinal properties, and other non-edible uses botanical description and common and vernacular names to help in plant identification medical and scientific glossaries.
Uncaria gambier(Hunter)Roxb. extract
Background: Osteoarthritis (OA) is a chronic debilitating degenerative joint disease characterized by cartilage degradation and synovial inflammation exhibited by clinical symptoms such as joint swelling, synovitis, and inflammatory pain. Present day pain relief therapeutics heavily relies on the use of prescription and over the counter nonsteroidal anti-inflammatory drugs as the first line of defense where their long-term usage causes detrimental gastrointestinal and cardiovascular-related side-effects. As a result, the need for evidence based safer and efficacious alternatives from natural sources to overcome the most prominent and disabling symptoms of arthritis is a necessity.
Materials and Methods: Describe the anti-inflammatory and analgesic effect of UP3005, a composition that contains a standardized blend of two extracts from the leaf of Uncaria gambir and the root bark of Morus alba in carrageenan-induced rat paw edema, abdominal constriction (writhing’s) and ear swelling assays in mouse with oral dose ranges of 100–400 mg/kg.
Results: In vivo, statistically significant improvement in pain resistance, and suppression of paw edema and ear thickness in animals treated with UP3005 were observed compared with vehicle-treated diseased rats and mice. Ibuprofen was used a reference compound in all the studies. In vitro, enzymatic inhibition activities of UP3005 were determined with IC50 values of 12.4 μg/ml, 39.8 μg/ml and 13.6 μg/ml in cyclooxygenase-2 (COX-1), COX-2 and lipoxygenase (5-LOX) enzyme activity assay, respectively.
Conclusions: These data suggest that UP3005, analgesic and anti-inflammatory agent of botanical origin with balanced dual COX-LOX inhibition activity, could potentially be used for symptom management of OA.
Uncaria gambir (W. Hunter) Roxb: From phytochemical composition to pharmacological importance
Purpose: To present an overview of the ethnopharmacology, phytochemistry, and pharmacological effects of the ‘wonder’ plant, Uncaria gambir (W. Hunter) Roxb.
Methods: The literature search for information on phytochemical composition and pharmacological importance of U. gambir was undertaken using diverse electronic search engines, including Google, Scopus, Web of Science, scientific literature, and databases (Pubmed, Springer and Science Direct). Other relevant literature sources include books, book chapters, conference papers, theses, and other scientific publications.
Results: Uncaria gambir Roxb possesses significant medicinal potentials as an antioxidant, anthelmintic, antibacterial, anti-diabetic, and for the management of osteoarthritis. Interest has increased among researchers for the utilization of this plant in complementary medicine, for example, to relieve sore throat, spongy gum, and dysentery, to treat atherosclerosis and obesity, and to prolong sexual intercourse.
Conclusion: Uncaria gambir demonstrates significant pharmacological properties. This review will be useful for prospective research and development of this ethnomedicinal plant into potentially valuable health products.
Background: Uncaria gambir (local name: gambir) is a plant native to Sumatera, Malaya and Borneo. This plant is potential as local wisdom for therapeutics. In Sumatera, gambir was used as a traditional treatment for fever, diarrhoea, diabetics and wound healing.
Aim: To explore the efficacy of gambir extract on TNF alpha level, prostaglandin E2 level, lesson area, body weight, lipid profile and leptin level in Wistar rat-model gastritis.
Methods: This study was an experimental study, with a pre-post-test control group design. The subjects in this study were 30 male rats, 8 weeks old, weight 150-200 gram. Rats were administered with gambir extract at the dose of 20, 40 and 80 mg/kg BW/day for 3 days. Gambir was extracted by maceration methods. Statistical analysis was performed by SPSS 18.
Results: Gambir extract at the dose of 80 mg/kg BW exhibited the highest efficacy in reducing TNF alpha level, lesion area and increasing prostaglandin E2 level compared to gambir extract at doses of 20 mg/kg BW, 400 mg/kg BW, negative control, and positive control.
Conclusion: Gambir extract was effective in reducing TNF alpha level, lesson area, and increasing prostaglandin E2 level in Wistar rat-model gastritis.
Uncaria tomentosa (cat’s claw)
natural anti-inflammatory agents for pain relief
The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions.
This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use.
Urtica dioica (aerial)
antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models
Objective: This study was aimed to examine the antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models.
Materials and Methods: Hydroalcoholic extract of the plant leaves was prepared by percolation method. Male Swiss mice (25-35 g) and male Wistar rats (180-200 g) were randomly distributed in control, standard drug, and three experimental groups (n=6 in each group). Acetic acid-induced writhing, formalin test, and carrageenan-induced paw edema were used to assess the antinociceptive and anti-inflammatory effects.
Results: The extract dose-dependently reduced acetic acid-induced abdominal twitches. In formalin test, the extract at any of applied doses (100, 200, and 400 mg/kg) could not suppress the licking behavior of first phase while doses of 200 and 400 mg/kg significantly inhibited the second phase of formalin test. In carrageenan test, the extract at a dose of 400 mg/kg significantly inhibited the paw edema by 26%.
Conclusion: The results confirm the folkloric use of the plant extract in painful and inflammatory conditions. Further studies are needed to characterize the active constituents and the mechanism of action of the plant extract.
Purpose: To develop and characterize an herbal gel prepared from methanol root extract of Urtica dioica (Urticaceae) (Stinging nettle) for the treatment of arthritis in mice.
Methods: A methanol root extract from Urtica dioica was prepared, and a gel was then prepared using Carbopol 934. The prepared gel was subjected to various physical tests (color, appearance, pH, texture, viscosity) and in vivo evaluation, including primary skin irritation, analgesic, and anti-inflammatory tests, in arthritic mice and compared with 2 % indomethacin gel, which was used as standard.
Results: The prepared herbal gel was of light gray color with a smooth texture. It showed a pH of 7.1 and a viscosity of 21.2 cps. The gel exhibited pseudoplastic rheology, as evidenced by shear thinning with increased shear rate. It was non-irritating to the skin in primary skin irritation test in mice and showed 55.05 % inhibition of paw edema in a carrageenan-induced hind rat paw edema model, comparable to that of the standard gel (53.93 %), after 24 h. The gel showed 58.21 % analgesia, versus 61.19 % analgesia for the indomethacin gel standard in writhing test.
Conclusion: The topical gel from methanol root extract of U. dioica may be an efficacious and safe alternative to non-steroidal anti-inflammatory drugs in the treatment of rheumatoid arthritis but this requires further investigations to ascertain its safety and clinical efficacy.
antioxidant, antimicrobial, antiulcer and analgesic activities of nettle (Urtica dioica L.)
In this study, water extract of nettle (Urtica dioica L.) (WEN) was studied for antioxidant, antimicrobial, antiulcer and analgesic properties. The antioxidant properties of WEN were evaluated using different antioxidant tests, including reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. WEN had powerful antioxidant activity. The 50, 100 and 250 μg amounts of WEN showed 39, 66 and 98% inhibition on peroxidation of linoleic acid emulsion, respectively, while 60 μg/ml of α-tocopherol, exhibited only 30% inhibition. Moreover, WEN had effective reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities at the same concentrations.
Those various antioxidant activities were compared to standard antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), quercetin, and α-tocopherol. In addition, total phenolic compounds in the WEN were determined as pyrocatechol equivalent. WEN also showed antimicrobial activity against nine microorganisms, antiulcer activity against ethanol-induced ulcerogenesis and analgesic effect on acetic acid-induced stretching.
In recent years a lot of the scientific interest has been concentrated on the identification of factors among low cost herbs that can be helpful in improving the health of humans. A shocking feature of herbal analysis has been that rarely any rare, exotic and exquisite plant has proved more fascinating. Typically some common, less familiar, and disdained weed have been discovered to possess undreamt of virtues. Urtica dioica is a weed and its seeds, leaves and even roots are used for medicinal purpose.
It is a sensible reservoir of micronutrients and nutritional elements which leads us to focus our study on this herb. Despite of being wholesome, leaves are easily digested and high in minerals (especially iron), vitamin C and pro-vitamin A. U.dioica is used as both medicine and food in many countries particularly in Mediterranean region because of being widespread and having conjointly exceptional biological activities. This comprehensive review is an effort to summarise the recent data on nutrition, pharmacological and clinical effects of U. dioica keeping in view the increased demand by patients to use natural products with antioxidant activity, anti diabetic activity and having potential for treatment of inflammatory diseases.
The review of nutritional properties is also an important aspect as every person needs general nutritional support in order to stay well or become optimally healthy. This review provides an overview of U. dioica in relation to antioxidant activity, anti diabetic activity, antimutagenic activity, antimicrobial activity, analgesic effect and treatment of inflammatory diseases that promotes its use.
Vaccaria segetalis (Neck.) Garcke seed extract
analgesic and anti-inflammatory effects of hydroalcoholic extract isolated from Semen vaccariae.
Semen vaccariae, the seeds of Vaccaria segetalis (Neck.) Garcke, is usually used as an important medication for female mammary gland diseases; it has also been used to promote lactation for centuries in China. The purpose of this work was to evaluate the analgesic and anti-inflammatory effects of hydroalcoholic extract from semen vaccariae (HESV) with oral doses of 50, 100 and 200mg/kg⋅bw in mice and rats. We observed that the HESV could effectively inhibit acetic acid-induced abdominal contraction and could elevate the latency time to thermal stimuli in the hot-plate test in mice. In the xylene-induced ear-swelling test in mice, HESV could suppress the ear swelling. Additionally, HESV could significantly decrease the peritoneal capillary permeability and leukocyte infiltration in mice induced by the intraperitoneal injection of acetic acid. HESV also significantly reduced paw thickness 2-4 hours after the injection of carrageenan in the carrageenan-induced rat paw edema test.
This study was the first to demonstrate that the oral administration of HESV might play an important role in the process of analgesia and anti-inflammation, supporting its use for female mammary gland diseases in traditional medicine.
Auricular Acupressure for analgesia in Perioperative Period of Total Knee Arthroplasty
Objective: We examined whether auricular acupressure (AA) can alleviate postoperative pain and decrease narcotic consumption and its adverse effects for osteoarthritis patients after total knee arthroplasty (TKA).
Design: A prospective, randomized, sham control trial comparing AA and a sham control.
Setting: Department of Orthopedics, the first Hospital affiliated to Zhejiang University of Traditional Chinese medicine, Hangzhou, China.
Subjects: Ninety patients with degenerative osteoarthritis undergoing TKA.
Interventions: The AA group received true AA by embedding vaccaria seeds at four specific AA points (knee joint, shenmen, subcortex, sympathesis) ipsilateral to the surgery site, while the control group received four nonacupuncture points on the auricular helix.
Outcome Measures: Visual analog scale (VAS), the consumption of analgesic via patient-controlled analgesia, the incidence of analgesia-related adverse effects, Hospital for Special Surgery scores (HSS), and range of motion (ROM) were recorded.
Results:VAS scores were similar at 12, 24, 36, and 48 h postsurgery (P > 0.05), but AA group scores were lower than those of the control group at 3, 4, 5, and 7 days (P < 0.05). Patients in the AA group consumed lower doses of analgesic than those in the control group after surgery (P < 0.05). The incidence of analgesia-related adverse effects in the AA group was lower than that in the control group (P < 0.05). Although HSS scores were similar in the two groups preoperatively and at 3 months postoperatively (P > 0.05), HSS scores 2 weeks postoperatively were higher in the AA group than in the control group (P < 0.05), but there was no difference between groups in ROM (P > 0.05).
Conclusion: Applying auricular acupoint acupressure in the perioperative period of TKA is favorable for alleviating postoperative pain, decreasing opioid consumption and its adverse effects, and promoting early rehabilitation. Also, this intervention has the advantage of lower costs, fewer complications, simple application, and high safety.
Veronica peregrina L extract
The drug treatment for neuropathic pain remains a challenge due to poor efficacy and patient satisfaction. Curcumin has been reported to alleviate neuropathic pain, but its clinical application is hindered by its low solubility and poor oral bioavailability. Curcumin diglutaric acid (CurDG) is a curcumin prodrug with improved water solubility and in vivo antinociceptive effects. In this study, we investigated the anti-inflammatory mechanisms underlying the analgesic effect of CurDG in the chronic constriction injury (CCI)-induced neuropathy mouse model. Repeated oral administration of CurDG at a low dose equivalent to 25 mg/kg/day produced a significant analgesic effect in this model, both anti-allodynic activity and anti-hyperalgesic activity appearing at day 3 and persisting until day 14 post-CCI surgery (p < 0.001) while having no significant effect on the motor performance.
Moreover, the repeated administration of CurDG diminished the increased levels of the pro-inflammatory cytokines: TNF-α and IL-6 in the sciatic nerve and the spinal cord at the lowest tested dose (equimolar to 25 mg/kg curcumin). This study provided pre-clinical evidence to substantiate the potential of pursuing the development of CurDG as an analgesic agent for the treatment of neuropathic pain.
Vicoa indica
Objective: To evaluate the antiinflammatory–analgesic property of the 4′,5,6-trihydroxy-3′,7-dimethoxy flavone from Vicoa indica DC using different agents and models.
Methods: antiinflammatory effects were produced by different inflammatory agents and after 4 hours the hind paw of the animals were sacrified and weighed in a torsion balance. analgesic effects were assessed by using different models and by acetic acid. In the former the analgesic effect was noted for a stipulated period of time and in the latter the writhings was counted for 15 minutes.
Results: The drug 4′,5,6- trihydroxy-3′,7-dimethoxy flavone at 50 mg/kg body weight was very effective in producing inhibition in both antiinflammatory–analgesic models.
Conclusion: This drug recorded consistent inhibitory and antiodema effects in the different agents used for the study.
Wilbrandia ebracteata
anti-inflammatory and analgesic effects of Cucurbitacins from Wilbrandia ebracteata
The anti-inflammatory and antinociceptive actions of the CH2Cl2 extract and semipurified fraction (F-III) from roots of Wilbrandia ebracteata Cogn. have been investigated in rats and mice. The CH2Cl2 extract (1-10 mg/kg, i.p.; ID50 5 mg/kg) and (3-30 mg/kg, p.o.; ID50 15 mg/kg) inhibited, in a dose-related manner, carrageenan-induced paw edema in rats. The subfraction (F-III) from CH2Cl2 extract and compounds isolated as cucurbitacin B and E also inhibited carrageenan-induced edema. The CH2Cl2 extract and F-III also exhibited significant analgesic action in acetic acid-induced pain in mice. In the formalin test, the CH2Cl2 extract (0.3-10 mg/kg, i.p.) and (3-30 mg/kg, p.o.) caused inhibition of the neurogenic (first phase) and inflammatory phase (second phase) of formalin-induced pain. However, the CH2Cl2 extract was more effective in relation to the second phase than in inhibition of the formalin-induced edema.
These findings suggest that CH2Cl2 extract has potent anti-inflammatory and analgesic action and that F-III and cucurbitacin B and E may account for these actions.
Willow bark
treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study
Purpose: herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain.
Subjects and Methods: We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain–free without tramadol for at least 5 days during the final week of the study.
Results: The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain–free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract.
Conclusion: Willow bark extract may be a useful and safe treatment for low back pain.
Xanthium sibiricum extract
Ethnopharmacological relevance: Xanthium sibiricum has been used as a traditional Chinese medicine for the treatment of appendicitis, bronchitis, arthritis, and other inflammatory ailments. However, its pharmacological activity related to an anti-inflammatory effect remain unknown. This present study aims to investigate the anti-inflammatory effect of methanol extracts of X. sibiricum roots (MXS), and to further determine its underlying mechanism of action in order to assess the medicinal value of X. sibiricum roots.
Materials and methods: To assess the anti-inflammatory activity of MXS in lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages, the production of nitric oxide (NO) was measured using the Griess reagent system. The levels of pro-inflammatory cytokines and mediators were quantified using an Enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Subsequently, immunoblotting analyses were employed to detect inflammatory mediators as well as to elucidate the underlying regulatory mechanisms suppressed by MXS.
Results: MXS inhibited LPS-stimulated NO production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 macrophages within the non-cytotoxic concentration range (50-400 μg/ml). In addition, mRNA and protein levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were significantly suppressed by MXS at the concentration of 400 μg/ml. Furthermore, MXS (200 μg/ml) clearly reduced the phosphorylation levels of the inhibitor of kappa Bα (IκBα) and signal transducer and activator of transcription 3 (STAT3), without affecting changes in the phosphorylation levels of mitogen-activated protein kinases (MAPKs). When five major components (betulin, betulinic acid, β-sitosterol, stigmasterol, and scopoletin) of MXS were separately investigated, stigmasterol and β-sitosterol seemed to play major inhibitory roles in the LPS-induced production of inflammatory mediators such as NO, IL-6, and TNF-α.
Conclusion: Our results demonstrate that MXS has an anti-inflammatory property in LPS-stimulated RAW 264.7 macrophages, and its anti-inflammatory activity is exerted by the regulation of nuclear factor-κB (NF-κB) and STAT3 signaling pathways.
Determination of TPA Content in Xanthium sibiricum Patrin ex Widder and Its anti-inflammatory effect
Objective: To establish a method of determining the content of total phenolic acid in Xanthium sibiricum Patrin ex Widder and investigate its anti-inflammatory action.
Methods: Chlorogenic acid was used as reference substance and diluted with 50% methanol solution to constant volume. The absorbancy was determined at wavelength of 426 nm by ultraviolet spectroscopy. With aspirin as positive control, the anti-inflammatory action of Xanthium sibiricum Patrin ex Widder was studied by ear swelling caused by xylene in mice.
Results: The average content of total phenolic acid in Xanthium sibiricum Patrin ex Widder was 5.22% and the RSD reached 0.17%. It could significantly relieve ear swelling caused by xylene in mice. Compared with normal saline, the result was of significant difference (P < 0.01).
Conclusion: The method was convenient and accurate, so it could be used to measure the content of total phenolic acid in Xanthium sibiricum Patrin ex Widder and explore its anti-inflammatory action.
Xanthium strumarium L.
The aim of this study was to fractionate an extract of Xanthium strumarium L. (EXS) and to investigate the anti-inflammatory and analgesic properties of the extract and its fractions. The ethanol extract of X. strumarium (EXS) was fractionated on the basis of polarity. Among the different fractions, the n-butanol fraction showed the highest anti-inflammatory activity in the croton-oil-induced ear edema test and furthermore reduced the number of writhings induced by acetic acid in mice in a dose-dependent manner. This indicates that the n-butanol fraction of X. strumarium possesses potent analgesic effects which are likely to be mediated by its anti-inflammatory activity.
Bioassay-guided fractionation of EXS led to the isolation and identification of ten caffeoylquinic acids and three heterocyclics by HPLC–DAD–MSn from the active n-butanol fraction, implying that the active compounds are polar in nature. The isolated caffeoylquinic acids could partially explain the antinociceptive effect of X. strumarium polar extract.
Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum)
Background: Zanthoxylum nitidum (Roxb.) DC., also named Liang Mianzhen (LMZ), one kind of Chinese herb characterized with anti-inflammatory and relieving pain potency, which is widely used to treat injuries, rheumatism, arthralgia, stomach pain and so on in China. But its mechanism related to the anti-hyperalgesic has not been reported. The aim of this study was to investigate the analgesic activity of Liang Mianzhen on mice with Complete Freund adjuvant (CFA)-induced chronic inflammatory pain. Meanwhile, the peripheral and central mechanisms of analgesic effect of Liang Mianzhen were further examined via observing the effects of Liang Mianzhen on the signal pathway associated with inflammatory induced hyperalgesia.
Methods: The inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After 1 day of CFA injection, the mice were treated with LMZ (100 mg/kg) for seven consecutive days, and the behavioral tests were measured after the daily intragastric administration of LMZ. The morphological changes on inflamed paw sections were determined by hematoxylin eosin (HE) staining. Changes in the mRNA expression levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor κB p65 (NF-κBp65) were measured on day seven after CFA injection by using real-time quantitative PCR analysis and enzyme linked immunosorbent assay (ELISA) method, respectively. Moreover, immunohistochemistry and western blotting were used to detect extracellular regulated protein kinases 1/2 (ERK1/2) and NF-κB signal pathway activation.
Results: The extract of LMZ (100 mg/kg) showed a significant anti-inflammatory and analgesic effect in the mice model. The paw edema volume was significantly reduced after the administration of LMZ compared to CFA group, as well as the paw tissues inflammatory damage was relived and the numbers of neutrophils in mice was reduced significantly. The CFA-induced mechanical threshold and thermal hyperalgesia value were significant improved with LMZ treatment at day three to day seven. We also found the mRNA levels of TNF-α, IL-1β, IL-6 and NF-κBp65 were down-regulate after 7 days from the LMZ treatment compared to CFA group. Meanwhile, LMZ significantly suppressed over-expression of the phosphorylation of ERK1/2 and NF-κBp65 in peripheral and central.
Conclusion: The present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level.
Objective: To provide the scientific evidence for expansion of medicinal parts of Zanthoxylum nitidum by comparing the effects of anti-contusion injury, analgesia and anti-inflammation of its root and stem.
Methods: The pharmacological effects between root and stem of Zanthoxylum nitidum were compared by observing the anti-injury effect in rats with injury struck by hammer. The analgesic effect in mice was evaluated by writhing test and hot plate test, and the anti-inflammatory effect on paw edema induced by carrageenan and granuloma induced by cotton pellet were investigated in rats.
Results: Both root and stem of Zanthoxylum nitidum relieved the exterior and histological symptoms of rats’ injury legs struck by hammer, decreased the numbers of mice’s writhing, enhanced pain threshold of mice on heat plate, inhibited the edema of rats induced by carrageenan, and suppressed the granuloma of rats induced by cotton pellet.
Conclusion: Stem of Zanthoxylum nitidum has similar effects of anti-contusion injury, analgesia and anti-inflammation with root of Zanthoxylum nitidum.
antinociceptive activity of Rhoifoline A from the ethanol extract of Zanthoxylum nitidum in mice
Aim of the study: Antinociceptive activity of Rhoifoline A (RA), a benzophenanthridine alkaloid obtained from the ethanol extract of Zanthoxylum nitidum, was evaluated in mice using chemical and thermal models of nociception.
Materials and methods: RA was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception.
Results: RA administered intraperitoneally at doses of 10, 20, 40 and 80 mg/kg exhibited significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin, and on thermal nociception in the tail-flick test and the hot plate test. RA neither significantly impaired motor coordination in the rotarod test nor did spontaneous locomotion in the open-field test. RA did not enhance the pentobarbital sodium induced sleep time. These results indicated that the observed antinociceptive activity of RA was unrelated to sedation or motor abnormality. Core body temperature measurement showed that RA did not affect temperature during a 2-hour period. Furthermore, RA-induced antinociception in the hot plate test was insensitive to naloxone or glibenclamide but significantly antagonized by L-NAME, methylene blue and nimodipine.
Conclusion: Therefore, it is reasonable that the analgesic mechanism of RA possibly involved the NO-cGMP signaling pathway and L-type Ca2+ channels.
Objective: To study whether crystal-8 exerts analgesic effect on the central nervous system,and to observe the relationship between crystal-8 and receptors.
Methods: A total of 32 SD rats were randomly divided into the 0.9% sodium chloride solution group, positive control group ( rotundine 2 mg·kg-1 ) , high dose of crystal-8 group ( 2 mg·kg-1 ) and low dose of crystal-8 group ( 1 mg · kg-1 ) . The changes of pain threshold were measured by the thermal stimulation test following intracerebroventricular (ICV) injection.The SD rats or mice were randomly divided into the 0.9% sodium chloride solution group, receptor tool medicine group ( including naloxone, reserpine, haloperidol, scopolamine) , crystal-8 group, receptor tool medicine plus crystal-8 group. The pain threshold was detected by the thermal stimulation test at 15, 30, 45, 60, 90, 120 min after dosing, then the influence of analgesic effect of crystal-8 on the neurotransmitter was observed.
Results: Compared with the 0.9% sodium chloride solution group, the pain threshold of rats was improved after taking the crystal-8 by intracerebroventricular (ICV) injection(P<0.01).Compared with the crystal-8 group, the naloxone plus crystal-8 group, the haloperidol plus crystal-8 group, the scopolamine plus crystal-8 group couldn’t increase the pain threshold, there was no significant difference among these groups(P>0.05).However, Reserpine plus crystal-8 group could significantly decrease the pain threshold in rats compared with the crystal-8 group(P<0.01).The analgesic effect of crystal-8 was interfered by reserpine.
Conclusion: The analgesic effect of crystal-8 may be involved in the central mechanism,which relates to monoamine neurotransmitters, but has nothing to do with the opioid receptor, M receptor, and the inhibition of central DA receptor.
Zingiber officinale
effects of a ginger extract on knee pain in patients with osteoarthritis
Objective: To evaluate the efficacy and safety of a standardized and highly concentrated extract of 2 ginger species, Zingiber officinale and Alpinia galanga (EV.EXT 77), in patients with osteoarthritis (OA) of the knee.
Methods: Two hundred sixty-one patients with OA of the knee and moderate-to-severe pain were enrolled in a randomized, double-blind, placebo-controlled, multicenter, parallel-group, 6-week study. After washout, patients received ginger extract or placebo twice daily, with acetaminophen allowed as rescue medication. The primary efficacy variable was the proportion of responders experiencing a reduction in “knee pain on standing,” using an intent-to-treat analysis. A responder was defined by a reduction in pain of ≥15 mm on a visual analog scale.
Conclusion: A highly purified and standardized ginger extract had a statistically significant effect on reducing symptoms of OA of the knee. This effect was moderate. There was a good safety profile, with mostly mild GI adverse events in the ginger extract group.
Evaluating the effects of ginger extract on knee pain,
stiffness and difficulty in patients with knee
osteoarthritis
The present study was aimed to evaluate the effects of ginger extract on knee pain, stiffness and difficulty in patients with knee osteoarthritis. 204 patients with knee osteoarthritis were enrolled in a randomized clinical trial. After a 1-week washing period, the groups received ginger extract (103 cases) or placebo (101 cases). A responder was defined by a reduction in pain of > 15 mm on a visual analog scale (VAS) or by 20% reduction in the mean score of each index of the Western Ontario and Mc Master Universities (WOMAC) criteria after 6 weeks. pain reduction according to VAS was more significant in ginger group than placebo (p<0.05).
Although pain reduction according to WOMAC was greater in ginger than placebo group, the difference was not statistically significant. reduction in morning stiffness and difficulty were statistically greater in the ginger than the placebo group (p<0.05). Also there was no difference between the two groups in side effects of therapy.
In conclusion, the results showed that ginger extract is effective in reducing pain, stiffness and difficulty in patients with knee osteoarthritis, therefore is recommended as a safe drug for these patients.
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$75.00 – $250.00
Tammy Bell –
Sciatic nerve pain. So, I’ve been dealing with sciatica pain for about 10 years on the right side of my butt cheek. I had lower back pain, burning down my leg, difficulty moving around in the bed before I would go to sleep. I would do some exercises to try and alleviate the sciatic pain…which only helped for a short time. At one time, I was going to the chiropractor 3 times a week to get adjusted for 3 months straight. I was even considering getting cortisone injections because the pain was so severe. I even did physical therapy a couple times a week…which didn’t help at all! The doctor prescribed anti-inflammation medication that would stop me from having (my) regular bowel movements. Hell, I had to stop that, because I wouldn’t have a BM for like 5 days and would end up taking a laxative. I just realized last night while lying in the bed, that my pain is GONE!!! I don’t know which blend that’s stopping the pain BUT I’m truly thankful that the pain is gone!!! I would wake up in the middle of the night because of the pain and now…NO MORE BACK PAIN!
Gavin, words couldn’t truly express the thankfulness that I’m feeling being pain free! Thank you so much for all that you and Kristine do!”
Trinity Blackwell –
My whole life I’ve struggled off and on with breathing, inflammation, allergies, digestion, brain fog, pain, energy, and focus. I’ve studied and trained and spent $$$$$. My health would improve and then go downhill again with any stressor. It came to an unsustainable place about a year and a half ago and I had to reboot and change everything. Again. I survived the ordeal and made a lot of progress, but there was still something missing.
After receiving my 11 blend challenge I started right away, which makes it hard to single out specific blends. After a few days (3 or 4?) the first change I noticed was my ability to handle temperature changes and reduction of inflammation. I went to a hot yoga class, which usually is difficult and makes me feel sick. Instead, it was a breeze, my body was easy to move, and I felt energized and more alive. The next change I noticed was my mood and focus. Suddenly my head felt clear and dealing with teenagers, taxes and work felt straight forward and simple, instead of anxiety provoking and fatiguing. I had more energy to exercise, and I stopped needing to take naps midday. I also completed an 8 day water/electrolyte/blends fast and my first 4 day dry fast. Wow! I have done a lot of water and electrolyte fasting in the past but never like this. I could have kept going, but caution rather than hunger made me stop. I was absolutely not hungry and by day 8 I was maybe a little too enthusiastic and energetic for my family 😅.
Although it’s hard to differentiate which blends do the most for me I’d say my top 3 are Trinity, Autophagy,, and Thermo.
Of course, I took all these benefits for granted since it felt so natural and stopped the blends two different times, once for a week, and the second time for a few days. Only to notice my old experiences creeping up on me. No more. I’m a believer. Thank you Gavin for all your research, recommendations, work, and quick response to my questions.“
Joshua –
Hey Gavin, just wanna say man you’ve changed my life with these blends I’ve been taken for about 3 months I wanna say now and wow dude I don’t how u get ahold of these magical elixirs but I had like this weird pinching nag and a little lump near the neck and collar bone and ever since I’ve taken them it has eased the pain. I can just endure a lot and tolerate more bs I thought I couldn’t but anyways u definitely rock! Stay blessed!
Wern –
Listen up!! It took me 3 years to make the buying decision. In all honesty, I was skeptical and unsure of how good a human being can actually feel. For years I’ve been trying different things to try to get rid of afternoon fatigue, brain fog, and irritability. At the beginning of 2022 I started feeling very edgy and more tired than not.
Something led me back to Gavin. I wrote to him and received a response within minutes; rare to find such fast and direct communication from company owners these days! Especially at the scale at which this man operates.
I took a combo of Trinity, Nebula, Luteolin, Rewire, Autonomous, and Pine Pollen. Bam! What an introduction to Interstellar Blends. Everything that people has to say about the blends are spot on. The only difference is you only KNOW once you try them. Nobody can tell you have good this stuff is and how good you can feel until you’re on it. I feel happier, more excited, bolder, more confident, more open, and more chilled, all at the same time. AND I started making more money! Coincidence? Nope. Blends!
The sense of calm and focus you’re able to experience from the start of the day till the end is incredible. I remember writing to Gavin, telling him: “Holy $h*t man. This stuff is on another level. I feel clear-minded, but not high. I don’t know what more to say to you other than Thank You.”
I have to add that I have tried many nootropics such as modafinil (the most commonly known) which pretty much just put me on a buzz and gave me the jitters. There was some degree of clarity but nothing comes close to Trinity x Autonomous x Nebula. Zero buzz. Zero jitters. Even with high doses of coffee, I do not feel irritable anymore. Since starting 22/2 fasting with blends my body has changed in many ways. The most noticeable is a reduction of lower ab and back fat along with less joint pain and inflammation.
The entire Interstellar-experience is 5-star! I f$cklng love what Gavin has created. There is no substitute. None. Zero. I am grateful for finding you, brother. I thank you for your service, your time and, your dedication to bringing change to the world.
To anyone reading this, you CANNOT go wrong! Your life WILL change. Spend $100-$200 to start and I promise you, you will never ever look back.
Lisa A –
I was led to Gavin’s blends a couple of years ago while on a quest to do a successful long term fast. I found that he has the blends to not only suppress cravings but to go to the source and eliminate them. He also not only stands by his products but literally is available what seems to be an unattainable 24×7 when you might be experiencing a purge from your body while using PURGE and having trouble deciphering which bodily portal the elimination process is trying to use.
When using the blends exactly as directed the results are phenomenal! Even at times when admittingly my taking them in a half-assed approached has alleviated stress, knee injuries, hip pain (to the point I barely can walk and my husband screaming, “you need a new hip”)
Even while getting COVID (was not taking blends as I should, take the VICTORIOUS daily!) I started fasting and taking blends and the COVID went away along with the dreaded hair loss 3 months later. I have just turned 57 and at my annual physical my doctor said had he not known me he would have thought I was 20 years younger. I definitely attribute my sustained youth to Gavin and his dedication to his quality of blends and clients.
Ken H –
I began the Interstellar Blends journey just over a year ago now. Based on the recommendation of my 30 year old son. He had been using them for several months. To hear him speak of his ability to better focus and his clarity of thought throughout the day was enough to sell me on the products. He suggested an assortment of blends to start and we placed an order.
Once we received the shipment I had to delay the start due to carpel tunnel surgery on both hands. Pre operative instructions said to stop all supplements a week prior to my procedure. Surgery took place 10/19/21.
Interstellar journey commenced on 10/20.
My order consisted of ….Thermo, EKG, ALZ, ACB, VICTORIOUS, SENOLYTIC, TRINITY, SUPERNOVA, PEEL, SPICE, PARASLAYER, HELICO, HYPNOTIC, LUTEOLIN, AND THUNDER.
I have taken all of these each day for over a year now. Except when traveling.
I added 7 Sages a while back for the times I travel.
To say I was amazed at the speed of my recovery from surgery would be an understatement. Being a 65 yr old male who still works in the electrical construction industry my body has gotten pretty beat up over the years. Thanks to Gavins blends I often times feel like I am a 40 yr old again.
I am still able to hike and bike on a regular basis and after 4 rotator cuff repairs still play golf on a regular basis.
In a recent order Gavin thought to include a sample of a pain/inflammation neutralizer. I had never seen it on the website. I have been taking it twice a day in black coffee and grapefruit juice. The changes in my left knee and shoulder are quite remarkable. I do hope I can spot it on the menu for my next order.
Gavin your products are a blessing. I feel I will be a lifelong customer. Thank you Sir.
Patty –
I’ve been taking the blends for over a year. LET ME TELL YOU, these are by far the BEST thing I stumbled upon. I have always been into alternative medicine and am never willing to take what big Pharma is pushing on me. I am a retired Registered Nurse and have pushed back against Pharma my entire career…weird right but my eyes were opened.
I have suffered with arthritis, pain, low energy but feeling of impending doom, thinning hair, and high blood pressure. Let me tell you….I tried many supplements to try and reverse these symptoms and nothing worked. Again by the Grace of God, I came across Gavin and his life saving blends. What a game changer!!
Here’s my results. By taking Peel and Spice for Arthritis, I have function back in my wrists and pain is under control. Low Energy and impending doom? GONE with NEBULA and TRINITY…I have never felt so calm and let things pass in my entire life! I use to be high strung and everything effected me. After having what I think was COVID..(never got tested) I started loosing my hair. How disturbing to me. I have been taking the hair blend and is thankfully growing back. Last but not least, EKG has brought my blood pressure into normal range. At every annual physical, my blood pressure was so high sometimes they didn’t want me to leave the clinic. This is a game changer for me. So happy I’m not in the critical zone anymore.
I could go on and on about the blends. Purge, Glucose Blocker, Anti Adipogenic, Thermo, and Autophagy for loosing weight…OFF THE CHARTS. I lost 10 pounds and have kept it off for over a year.
This is getting long so just try them….you’ll never go back! Thank You Gavin so much for your life saving and beautiful blends. They are filled with Love.
Ms. Reyes –
I have been an Interstellar customer for over two years. Within that time, I have shared the “magic” of these blends with anyone I hear complaining about their aches and pains. Many just roll their eyes and change the subject, but a few have made snide remarks without even trying them first.
Well, one of my brother-in-laws was one of those who always had something negative to say. I’m not sure where all that snarkiness was coming from since he hadn’t nor would even try them. That was until 3 days ago. He felt sick and tested positive for covid.
Earlier on, Gavin had shared with us a protocol to combat that bug. Well, my brother-in-law was in so much pain that he finally accepted to try the blends. His fever had reached 103 and within 30 minutes of taking those blends, his temperature was down to 99.8. He is now a believer!
Thank you Gavin for always going above and beyond!! You are treasured more than you realize!!!
So all I can say to those who doubt… try and be amazed of the “magic” of Interstellar Blends!!
Treena Smith –
The Interstellar pain killer blend is amazing!! 🔥The Supernova Interstellar blend is incredible!! 🔥 I’ve suffered from migraine headaches my entire adult life. I was hit by a car at aged 8, that resulted in chronic inflammation in my right leg. Migraines and chronic inflammation are my life and I’ve learned to cope. When I began using Interstellar blends…it was simply out of curiosity. I read the reviews on all the Interstellar blends and wondered if Gavin’s customers were over hyping his products. I purchased Interstellar Supernova and was a given a free sample of the pain killer blends to also try. I wasn’t expecting mind blowing results; my history taught me to tread lightly when it comes to a solution for complete pain eradication.
Well…it’s been almost a month and I am mesmerized by all of the awesome results of the blends!!!! I can truly say my life has shifted for the better!! My migraine headaches have decreased to a level of zero, my energy has increased, the inflammation in my leg has drastically reduced. The Supernova, specifically has also curved my appetite and made my skin glow. I’ve been feeling extra sexy these days thanks to these blends!! Gavin, thank you for the experience of a life free of headaches and inflammation!! Gavin, you are incredible, gifted and kind!! Thank you for sharing these blends with the world!! ⭐⭐⭐⭐⭐
I’m now a permanent customer of the Interstellar Blends; I’ve already made my next purchase!
Tony R –
Magical Blend.
This is long overdue, so, here we go.
I found out about Interstellarplan from a forex trader named Shaun Lee from one of his ig posts when it was still on. I’m always into natural way of taking care of my own health without involving pharmaceuticals. I used to have headache when I was younger and went to search for natural remedies by looking at my lifestyle and find what is causing the headache. I never even want to take aspirin or pain killer.
So, long story short, I join Interstellar Blend tele channel and follow the discussions for a good couple of weeks before buying the blends. My first batch consist of Trinity, Rewire, Autonomous, Nebula, Matcha, Senolytic, Apigenin and Seven Sages. I do not set any expectation when taking the very first dose of the blend. But what happen in the next couple of hours was nothing short of MAGICAL. I feel very calm and can direct my focus and attention without fail (and for a long period of time). Everything I do that day feels effortless, everything just flows naturally. No procrastination.
Then I bought my second batch which consist of pine polen, Rewire, Autonomous, purge, and several other blends. Bear in mind, I’m currently struggling financially but managed to buy the blends – its all about priority. Also, thanks to Gavin’s generosity by giving massive discount continuously. About 50% discount on both orders. So, the “expensive” international shipping becomes negligible.
Then, 3 weeks ago I bought the third batch which include the Pain Blend (a prototype). This blend is simply another miracle. I took the Pain blend twice a day for 7 days. My back pain (due to HNP) was completely gone. I know this is not a placebo effect as I’ve been having this back pain for more than a decade. Hot yoga has been my go to cure for this back pain to fix the HNP and back bone alignment. Even with hot yoga, I can still feel the pain, although not everyday. The Pain blend completes the puzzle and eradicate the pain completely.
As a summary, the blend works wonders in many aspects of my life. Health is the primary one. I feel full of energy, don’t feel tired and have great mental clarity. What I write above is not sugar coat, its the reality. By the way, I lost about 6.5kg in 3 months (weight loss is not my goal when buying the blend but I know I will loose weight eventually). Oh . . don’t forget the 22/2 intermittent fasting protocol. I’m doing that too . . super easy.
Totsten Oberacker –
I dont know where to start…
I was reading many of the information (studies, reviews, product descriptions) for over an year now and was fascinated from the first moment i read all this amazing stuff on Gavins site. He dont want to sell only products, Gavin is looking on the whole thing with every little piece of the puzzle.
After one year of only looking (i dont had money to spent for at this time) i started with my first order.
EVERY DOLLAR I SPENT FOR IT WAS BEST INVESTET!!!
First i was ordering the challenge combo essentials and combined with fasting (i am on vegan keto with fasting for about 3 years now, BUT never had this amazing effects on the wellbeeing ever before).
Then i took the next step and ordered the stomach reset combo and the january special. MAN, this was the next level stuff i was wishing for the Last years.
Actually i am waiting for my next order (should be comming these days ;), the 25 mega blend combo, glucose blocker and Jing force
I NEVER WANT TO MISS THE BLENDS EVER AGAIN
I feel brain unfogged, amazing, happy, fearless, healthy, gut pain and bloatings are away, psoriasis is over 50% better and is going away week by week, i am selfconfident, stresslevel is down, i love life, less stress with my lovely wife, seeing everything clear and feel the BEST IN MY LIVE I EVER FELT.
My wife had lost her depression and panic attacks over 90%, stopped her depression-medication, feels amazing, loves the super tonic hair blend and our relationship is better than ever, relaxed and amazing.
I am a silent reader in the telegram group Gavin made for his custmers… Gavin is a man that stands to his words, helps people from his deepest heart with passion and love, he is loyal, tells the truth without fear.
He is really a man with a heart of gold and that is what you get when you take his advice and his products.
Gavin and his blends take the life of me and my lovely wife manu to absolutely lovely perfection.
I want to thank you from my deepest heart Gavin Robert McGowen
Thank you, thank you, thank you 🙂
Emily Davidd –
The blends are fantastic— everything they’re advertised as and more. The packaging is pretty too! Gavin answered all my questions promptly and fully— he shared a wealth of knowledge with me and directed me to numerous studies which I appreciate. The blends don’t taste that great, but man do they deliver! Best way to take them is to throw ‘em back like a shot. The only negative thing I can think of is I wish I found Gavin and his blends sooner. Would’ve saved me a lot of time, Frustration, pain, energy and money. His blends are worth every penny.
Suzanne Linskens –
I started the interstellar blends a few years ago. I was sick of running to multiple doctors to figure out solutions to my health issues. I have corrected multiple issues in the past few years by taking the blends Gavin developed. I have corrected my hashimotos disease, eliminated chronic back and knee pain. I add new blends periodically and they are all top notch! Gavin takes years to develop and perfect these blends. I am almost 47 and I have more energy and stamina than I had when I was in my
20s! The blends are legit…absolutely not “snake oil”.
KT –
Ascendance is absolutely amazing! I received my shipment today and I am beyond speechless. A backstory early this summer I started getting a dull throbbing pain in my scapula area. I thought I had just a sore muscle. I do TRX workouts 4-5 times a week and just kept working out through the pain. This kept getting more irritated but still didn’t think much of it. Fast track to three weeks ago. The pain became unbearable and started shooting down my arm into my fingers. Come to find out it was a pinched nerve in my neck. This pain has been debilitating. It hurt to do everything and let’s face it when you’re in constant pain, you tend to be the not so pleasant being around. The doctors gave me a light muscle relaxer and I could also take Advil which was suggested. I know this is not good on my liver so it was always only if unbearable would I take. I reached out to Gavin and he recommended Ascendance and Spice. I took the Ascendance for the first time today and went about my day. I started to realize there was no throbbing pain anymore. I was not wincing with every movement. I am amazed…shocked. I literally can’t believe it. This is an amazing blend for pain. This is a great tool to help me manage my pain, get through physical therapy and basically enjoy my day again. Thank you for such an awesome product!
Cary Duke –
“Hey you! Yeah, YOU.
I know you are reading this. I know you what you are thinking.
Because I had the same thoughts.
These people posting ridiculous results must be doing something different. Something I can’t do. They must have an unbelievable amount of will power.
Nope.
Not even close.
I’m just like you.
Probably older and more out of shape than you.
I DECICED to be healthy. I decided to change my eating and drinking habits.
That’s it!
That is the single biggest change I made.
I decided to be a person who eats healthy, doesn’t drink.
Results?
20 days
21.6lbs lost
No cravings
No alcohol (I was a daily drinker for far too long)
NO acetaminophen (I was up to 4 per day)
OMAD for 18 days straight with NO hunger or craving issues
NO pain
Blends: Trinity, Supernova, Pain Blend 2x day
ACV, lemon juice and salt 2x day
That’s it.
No secret diet. No exercise.
Nothing hard.
So, back to you. You still reading?
You want to make changes in your life?
Do you have a desire to feel better, have more energy, have no pain?
Start with deciding to BE that parson.
Then go live as if you already are that person.
Last, get Gavin Robert McGowen’s blends. They enhance your decision AND they simply work.”
————————
The pain blend is a winner!
Stats: Down 15.8lbs. Fasting 22/2. Strict Keto.
My biggest issue going in was chronic knee pain. It’s been so much better. I can climb the stairs without any pain. More importantly, I can descent the stairs like a normal person. No crab crawling sideways one step at a time.
My energy level is much improved. My cognitive ability is much improved.
There has been a tremendous difference in only two weeks.
Totally Awesome, Gavin Robert McGowen
Blends taken: Pain, Trinity, SuperNova
———–
PAIN BLEND: “My Report One Full Week:
Details: 60, very bad knees, overweight. Stairs to my office and bedroom.
I started doing IF and have moved all the way to 23/1 in a week. No issues with diet. Doing keto. Eating clean. No alcohol. Cut way back on soda (phasing it out).
Coffee in the am with Trinity, Supernova and the Pain Annihilator. I’m also taking ACV.
Mid-day a small cup of double chai tea w/blends and ACV
Eating keto meal when window opens. Hunger is getting less and less during the day. Always manageable. ACV one hour after meal.
I am down 12.8 pounds. One Week.
Energy level is increasing.
Sleep is deeper.
The biggest noticeable factor?
There are 2
The first is awaking w/o feeling pain in the knees.
The second is walking down the stairs like a normal person ie just walking down them. NO PAIN.
This is really fantastic!”
Jenny C –
This is an awesome Combo-especially with the Pain Blend included! I was lucky enough to try the Pain Blend for a whole month before it was even released-which I am eternally grateful for. I have pretty severe psoriatic arthritis and was on a lot of medications that were only masking my symptoms and also making me sicker….about a month ago Gavin asked if anyone would like to test the Pain Blend–I JUMPED!! Best decision I’ve made in years. I know it may sound slightly dramatic–but its really not—THIS BLEND CHANGED MY LIFE!!!!! I am OFF all my medicine never to return to it again, I can literally jump out of the bed in the mornings, which I could NOT do even two months ago. Do you understand how awesome that is?? I feel truly Amazing.
The other Blends are amazing too! I love Nebula-it really helps me at work. I am very shy/Timid and when I take Nebula in the mornings before work…–WOW! Game Changer! People literally don’t “get to me” when I’m on this Blend.
The other new Blend is Rewire! I had very good results when I first took it-it lights up your Brain. I gave the rest to my mom to help her-and she loves it too! She says it really makes her not as hungry as she normally would be (also makes it where she doesn’t crave ‘bad foods’).
Trinity was the first Blend I every tried! It helps so much with calming me and my Anxiety. It’ll always hold a special place in my heart.
Autonomous will help you be laser focused on getting stuff done!
All the Blends in this package will help you have a better life–in ALL aspects of your Life!!
———————-
My 30 Day Challenge with the Pain Blend ended yesterday!!
I feel like a different person! Virtually all my pain is gone. I have not been on medication for the full 30 days-and I will NOT be going back to it, because there is no need! The Pain Blend did 100 Times BETTER than any medicine I was ever subscribed!
My main focus was to get rid of pain(accomplished)—-but as an added bonus I lost 20.6 Pounds!
Thank you Gavin-so much! Words can’t really express how happy I am!!!!!!!!!!
——————-
Where do I even begin??
First I would like to say Thank You to Gavin and all of his team for the Amazing Products, Shipping and customer service they provide!
These Products have improved my whole life…in such a short time! He is the real deal, you can tell him your ailments or what you want to get better at (such as confidence or no anxiety, etc) and he can match you with the best Blends to help you!!
I have Psoriatic Arthritis and its been getting worse and worse, but luckily Gavin has a Blend for that. 😉 I signed up to do 30 days with the Pain Blend Prototype along with several other blends; happy to say the pain has went away! This alone will make me a customer for LIFE. I am off all of my pain medications for arthritis (which only masked the pain and made me so sick), and replaced it with this particular blend! Its amazing!
My parents say they see such a difference in me! My moods are better and my mom said she can just “hear in my voice” how much better I am feeling.
These Blends are truly a LIFE SAVER. I can’t wait to see all the new and exciting things that will be coming out in the next few years.
YOU owe it to your mind and body to start these Blends and live an Interstellar Life!
—————–
Hi Gavin! I’m at my ‘last’ TEN DAYS!! These past 20 days have been awesome! I am back to loving fasting, and I feel so so SO good from the Pain Blend! I really cannot thank you enough!!
It means the world to me. I love that I am off all my medication (which quite frankly didn’t help much at all-just slightly took the pain edge off) The Pain Blend blows everything I took out of the water!!
Julia Bienkowski, LPC –
Gavin has knocked it out of the park again with his incredible non-opioid pain relieving blend, Ascendance! I have struggled for years with debilitating flare ups of musculoskeletal pain and inflammation and multiple herniated discs as a result of car accident several years ago. I have tried every natural pain relieving supplement to manage the pain, but have never experienced relief so quickly and effectively until Ascendance. After 2 days of taking Ascendance, my back pain was gone entirely and my full range of motion restored. Effective non narcotic pain relief at last! This is truly a miracle product. Thanks Gavin!
Rich Ryan –
Amazing Blend for Pain!
The folks at Interstellar Blends knock it out of the park again!
I do big doses of the blends I get to try, as I want to feel the maximum effect. So I did 1/2 tsp of Ascendance (regular dose is 1/4-1/8 tsp) and I could feel the effects within 15 min.
Ascendance made me feel high and highly positive! It boosted my mood into the clouds.
I’ve been managing arthritis pain in my hands and ankles for years with Spice and Peel blends (Mom has Rheumatoid and both parents have Osteo Arthritis). With those blends the pain and swelling was down to a minimum. Just mild twinges here and there. With Ascendance however, the pain completely disappeared. I didn’t feel a twinge for the entire 30 days I was on it.
I’ve also been managing back pain from years of construction work with the blends as well. The stiffness of a morning back was 98% gone with Ascendance. I could barely feel any soreness or stiffness at all. It just vanished! And without any opioids either!
If you’re getting advanced in years or struggling with chronic pain, you definitely need to try this blend. With this blend it’s back to smooth sailing again!
Bravo!
Leslie Spry –
My sister, Tonia kept telling me about the blends and told me about Ascendance.
I’ve been suffering from pain for years and it’s something I thought I would just have to live with, though I was taking pain meds.
I received my blends on a Friday and started taking them the next day. I felt relief the same day. Within two days I felt a huge difference! I take Ascendance with 2 oz of coffee 3 x per day.
I Highly recommend Ascendance for anyone suffering with pain and inflammation.