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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.
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
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
Attenuating effect of Acorus calamus extract in chronic constriction injury induced neuropathic pain in rats: an evidence of anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory effects
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.
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
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
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 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
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
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
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 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.
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.
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
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)
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
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.
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
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
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.
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.
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.
Conolidine; an indole alkaloid derived from bark of Tabernaemontana divaricate
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
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 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.
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 122.43Î¼g/mL while the IC50 value for the reference ascorbic acid was 147.87Î¼g/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.
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 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.
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 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
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
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.
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.
Erythrina variegata Linn.peel extract
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.
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.
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).
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 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.
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
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.
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.
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.
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 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
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.
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.
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.
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
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
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
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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 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.
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
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
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
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.
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.
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
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.
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)
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.
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
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.
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.
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.
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.
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