Isolation, invitro, invivo anti-inflammatory, analgesic and antioxidant potential of Habenaria plantegania Lindl.

Habenaira plantaginea belong to orchid family which is native to Asia. Members of this family are commonly famous for the cure of pain and inflammation. To date, no research was found on isolation of compounds from this plant for the treatment of inflammation and analgesia nor has been published to our knowledge. The purpose of this study was to evaluate an analgesic, anti-inflammatory and anti-oxidant activity of the isolated compound from the most potent chloroform sub-fraction and the isolated compounds form the habenaria plantaginea. Anti-inflammatory analgesic and antioxidant potential of the various chloroform sub-fractions and isolated compounds from the most potent sub-fraction (HP-1 & HP-1) were screened for their in vitro enzymatic assays. Furthermore, prior to in-vivo investigation, the isolated compounds were subjected for their toxicity study. The potent compound was then examined for acetic acid-induced writhing, hot plate test, carrageenan-induced inflammation assays. Further various phlogistic agents were used for the evaluation of mechanism. In the COX-2 inhibitory assay the chloroform sub fraction Cf-4 demonstrated excellent activity as compared to the other sub-fraction with 92.15% inhibition. The COX-2 enzyme make prostaglandins which are directly involved in inflammation. Likewise against 5-LOX the Cf-4 was the most potent sub-fraction with IC50 3.77 µg/mL. The 5-LOX catalyzes the biosynthesis of leukotrienes which is a group of lipid mediators of inflammation derived from arachidonic acid. Free radicals can induce inflammation through cellular damage while chronic inflammation generates a large number of free radicals, whose eventually lead to inflammation. In antioxidant assays the Cf-4 fraction was displayed excellent results against ABTS, DPPH and H2O2 free radical with 88.88, 77.44, and 65.52% inhibition at highest concentration. Likewise, the compound HP-1 demonstrated 88.81, 89.34 and 80.43% inhibition while compound HP-2 displayed 84.34, 91.52 and 82.34% inhibition against ABTS, DPPH and H2O2 free radical which were comparable to the standard drug ascorbic acid respectively. This study's findings validate the use of this species as traditional use.

Analgesic and Anti-Inflammatory Activities of 80% Methanol Extract and Solvent Fractions of Ehretia cymosa Thonn (Boraginaceae) Leaves in Rodents.

Background: Ethnobotanical studies in various districts of Ethiopia reported that Ehretia cymosa (E. cymosa) is used for the management of headache, abdominal pain, arthritis and rheumatism. However, there is no scientific investigation done so far to confirm these traditional claims. Thus, the aim of this study was to assess the analgesic and anti-inflammatory effects of the 80% methanol extract and fractions of E. cymosa leaves. Methods: The dried and pulverized leaves of E. cymosa were soaked with 80% methanol to obtain a crude extract. Fractionation was done using chloroform, ethyl acetate and water by a soxhlet apparatus. The analgesic effects of the crude extract and solvent fractions were assessed using acetic acid-induced writhing and hot plate tests whereas anti-inflammatory activities were investigated using carrageenan-induced paw edema and cotton-pellet-induced granuloma models. Results: In all the tested doses, the 80% methanol extract and solvent fractions revealed substantial (p < 0.001) analgesic activities in acetic acid induced writhing test. In the hot plate method, all the tested doses of E. cymosa crude extract and the solvent fractions produced significant analgesic activities (p < 0.05). In the carrageenan-induced acute inflammation model, all tested doses of the crude extract and solvent fractions resulted in a significant decline in paw edema. The 80% methanol extract and solvent fractions of E. cymosa at all the tested doses significantly reduced inflammatory exudates and granuloma mass formations (p < 0.001). Conclusion: From the results of this investigation, it can be stated that 80% methanol extract, aqueous, ethyl acetate and chloroform fractions of E. cymosa exhibited considerable analgesic and anti-inflammatory activities, supporting the plant's traditional use as a remedy for a variety of painful and inflammatory conditions.

Expression of oxytocin in hypothalamus and reduction of nociceptive stress following administration of Kamikihi-to in female rats.

Hypothalamo-neurohypophysial oxytocin (OXT) plays an essential role in reproduction and in several socio-physiological functions, including stress reduction, anxiety relief, feeding suppression, social recognition, and trust building. Recent studies suggest that the central OXT system is also involved in antinociceptive and anti-inflammatory functions. Kamikihi-to (KKT), a Japanese traditional herbal (Kampo) medicine composed of 14 herbal ingredients, is clinically prescribed for patients with psychological symptoms, including anxiety, depression, and insomnia, and it has been associated with OXT expression. We investigated the antinociceptive response and OXT expression according to sex and the effects of KKT pre administration in a rat model. We found that nociceptive responses measured via the hot plate and formalin tests were attenuated following the administration of KKT-enriched feed for 4 weeks. The observation of mRFP1 fluorescence in OXT-mRFP1 transgenic rats revealed that KKT-administered rats showed increased expression of OXT in the magnocellular and parvocellular paraventricular nucleus of the hypothalamus. Food intake in the KKT-pre-administered group significantly decreased after cholecystokinin (CCK)-8 administration. Our results suggest that KKT is involved in the attenuation of nociceptive stress in female rats by enhancing the expression of OXT in the hypothalamus.

Synthesis and Investigation of the Analgesic Potential of Enantiomerically Pure Schiff Bases: A Mechanistic Approach.

Schiff bases are a class of organic compounds with azomethine moiety, exhibiting a wide range of biological potentials. In this research, six chiral Schiff bases, three 'S' series (H1−H3) and three 'R' series (H4−H6), were synthesized. The reaction was neat, which means without a solvent, and occurred at room temperature with a high product yield. The synthesized compounds were evaluated for analgesic potential in vivo at doses of 12.5 and 25 mg/kg using acetic-acid-induced writhing assay, formalin test, tail immersion and hot plate models, followed by investigating the possible involvement of opioid receptors. The compounds H2 and H3 significantly (*** p < 0.001) reduced the writhing frequency, and H3 and H5 significantly (*** p < 0.001) reduced pain in both phases of the formalin test. The compounds H2 and H5 significantly (*** p < 0.001) increased latency at 90 min in tail immersion, while H2 significantly (*** p < 0.001) increased latency at 90 min in the hot plate test. The 'S' series Schiff bases, H1−H3, were found more potent than the 'R' series compounds, H4−H6. The possible involvement of opioid receptors was also surveyed utilizing naloxone in tail immersion and hot plate models, investigating the involvement of opioid receptors. The synthesized compounds could be used as alternative analgesic agents subjected to further evaluation in other animal models to confirm the observed biological potential.

Antinociceptive activity of puberulin and choisyine from ethanol extract of Choisya ternata Kunth var. Sundance.

Choisya ternata Kunth variety Sundance (CTS) is a plant used in traditional medicine in North America, especially in Mexico. The present study evaluated the antinociceptive activity of the crude ethanolic extract of CTS leaves and tested its isolated compounds puberulin (Pu) and choisyine (Ch). An antinociceptive effect was observed after treatment with CTS extract and the isolated compounds Pu and Ch. Mice orally pre-treated with CTS extract (10, 30 or 100 mg/kg), Pu or Ch (0.3, 1 or 3 mg/kg) were less sensitive to chemical and thermal algesic agents in different animal models (formalin-, glutamate- and capsaicin-induced licking response tests and hot plate test). In addition, an antagonist of the opioid receptor was able to reverse the antinociceptive effect observed for the CTS extract and the isolated substance Ch, but it did not inhibit the effect of Pu. The cholinergic pathway was found to be involved in this antinociceptive effect for the CTS extract and Ch but has no participation in the Pu antinociceptive activity.

Anti-nociceptive, anti-inflammatory and possible mechanism of anti-nociceptive action of methanol leaf extract of Nymphaea lotus Linn (Nymphaeceae).

The leaf of Nymphaea lotus has been used traditionally for the management of pain and inflammatory diseases. The methanol leaf extract of Nymphaea lotus (NLE) was evaluated for possible anti-nociceptive and anti-inflammatory activities in rats and mice (at the doses of 250, 500 and 1,000 mg/kg) to investigate the existence of scientific basis for the folkloric use of the plant. The standard drugs used were piroxicam (10 mg/kg) and morphine (10 mg/kg). The possible pharmacological mechanism involved in the anti-nociceptive activity was also investigated. The acute toxicity was determined in mice and rats using method of Lorke. The anti-nociceptive activity was evaluated using acetic acid-induced writhing and hot plate tests in mice, while the anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema model in rats. The oral median lethal dose of NLE was found to be greater than 5,000 mg/kg in rats and mice. NLE demonstrated significant and dose-dependent protection against acetic acid induced writhes and increased the reaction time of mice in hot plate test. Pretreatment of the animals with naloxone (2 mg/kg) significantly (p < 0.05) attenuated the anti-nociception elicited by both NLE and morphine. NLE at the doses of 250 and 1,000 mg/kg significantly (p < 0.05) decreased rat paw edema at the 2nd hour in the carrageenan-induced paw edema test. The result of the study revealed that Nymphaea lotus possesses anti-nociceptive activities which may be mediated via the opioidergic system as well as mild anti-inflammatory activities thus providing scientific basis for the use of the plant in the management of pain and inflammatory diseases.

Pharmacological investigation of analgesic and antipyretic activities of methanol extract of the whole part of Aeginetia indica.

ETHNOPHARMACOLOGICAL RELEVANCE: Aeginetia indica (Linn.), commonly known as aankuri bankuri, guan-jen-huang, forest ghost flower, dok din daeng, dapong tubo; is a root parasitic plant of the Orobanchaceae family native to South and South-East Asian region. Different parts of the plant are traditionally used to treat fever, pain, inflammation, arthritis, cough, diabetes, and chronic liver disease. Local practitioners often recommend this plant as a folk remedy for dermal swelling, painful menstrual periods, wounds, and knee pain. However, the antipyretic and analgesic activity of A. indica have never been investigated. AIM OF THE STUDY: The present study was aimed to evaluate the analgesic and antipyretic potential of Aeginetia indica plant extract to verify its effectiveness as reported in traditional uses. MATERIALS AND METHODS: Preliminary phytochemical analysis of Aeginetia indica crude extract was performed using previously established methods and antioxidant capacity was determined by phosphomolybdenum assay. In vivo analgesic activity of Aeginetia indica methanol extract (AiME) was evaluated by acetic acid-induced writhing test, formalin-induced paw licking test, and hot plate test model. The antipyretic activity was studied in Baker's yeast induced pyrexia model. RESULTS: Phytochemicals screening revealed cardiac glycosides, saponins, phenols, tannins, and flavonoids in the crude extract of Aeginetia indica. Total phenolic and flavonoid content were recorded as 101 ± 1.1 mg GAE/g of the extract and 35 ± 0.8 mg QE/g of the extract, respectively. The total antioxidant capacity observed in phosphomolybdenum assay was 68.3 ± 1.3 mg ascorbic acid equivalent per gram of the extract. AiME showed significant dose-dependent analgesic activity against acetic acid-induced writhing, formalin-induced paw licking, and hot plate pain model. A higher dose of A. indica (200 mg/kg) produced significant (P < 0.001) inhibition of writhing by 69% whereas, standard aspirin showed maximum 85.6% inhibition. AiME at all doses showed a significant (P < 0.001) decrease of paw licking time in both early neurogenic and late inflammatory pain phase of formalin-induced licking test. In the hot plate test, AiME at a 200 mg/kg dose produced antinociceptive activity (55.18%) higher than the standard ketorolac (49.88%) at 1 h. However, after 2 h, ketorolac showed a maximum effect of 62.66% and AiME 200 mg/kg showed a 60.24% effect. A significant (P < 0.001) reduction of rectal temperature (4.54 °F↓) was recorded for AiME 200 mg/kg, which was higher than the standard paracetamol (3.86 F°↓) after 24 h of treatment. CONCLUSION: The in vivo investigational studies' results demonstrated promising analgesic and antipyretic activities of A. indica, which supported the claim of its folk uses.

Myrciaria dubia Juice (camu-camu) Exhibits Analgesic and Antiedematogenic Activities in Mice.

The Myrciaria dubia (Myrtaceae) fruit is traditionally used to treat malnutrition due to its high levels of vitamin C and phenolic compounds. Because of its composition, this plant is very promising in the research of novel natural treatment for pain disorders. This study analyzed the phytochemical profile of M. dubia juice and assessed its antinociceptive and antiedematogenic potential. The phytochemical profile was determined through high-performance liquid chromatography (HPLC), the oral antinociceptive effect of M. dubia 50% juice (Md50) was evaluated by formalin, hot plate and Complete Freund's Adjuvant tests and the antiedematogenic activity by paw edema. HPLC revealed the presence of ascorbic acid, rutin, and ellagic acid as major compounds. Md50 showed an antinociceptive effect in the acute and chronic phases of the formalin test. In the hot plate test, Md50 also induced an antinociceptive effect of 0.5 up to 6 h, showing antinociceptive and antiedematogenic potential without changing the spontaneous locomotion of animals. All protocols were submitted and approved by the Ethics Committee for use of Animals of the Lutheran University of Brazil (protocol No. 2013-30P).

Evaluation of Analgesic and Anti-Inflammatory Activities of 80% Methanol Root Extract of Echinops kebericho M. (Asteraceae).

BACKGROUND: Pain and inflammation are the major devastating health problems commonly treated with traditional medicinal plants in Ethiopia. Echinops kebericho M. (Asteraceae) is the one which is frequently used to treat pain and inflammation by traditional healers in Ethiopian folk medicine. However, the plant has not been scientifically evaluated for its traditionally claimed use. The present study aimed at the investigation of analgesic and anti-inflammatory activities of 80% methanol root extract of Echinops kebericho M. in mice model. METHODS: Successive maceration was used as a method of extraction using solvents of increasing polarity: methanol and water. After extraction of the roots with 80% hydro methanol, the crude extract was evaluated for its peripheral and central analgesic activities using acetic acid-induced writhing test and hot plate method, respectively, while its anti-inflammatory activity was evaluated using carrageenan- and formalin-induced paw edema. The extract was evaluated at 100, 200 and 400 mg/kg doses. The positive control groups were treated with ASA 150 mg/kg for writhing test, morphine 10 mg/kg for hot plat method, indomethacin 25 mg/kg and diclofenac 10 mg/kg for paw edema tests and vehicle, distilled water (10 mL/kg) treated mice were assigned as negative controls. All treatment administrations were performed orally. RESULTS: E. kebericho extract at all test doses showed statistically significant antinociceptive activity in both chemicals-induced peripheral and thermal-induced central pain in a dose dependent manner (p < 0.01 and p < 0.001). The greater analgesic activity was observed by the maximum dose of the extract (400 mg/kg) in both acetic acids-induced writhing test (57.84%) and hot plate method (69.40%). The effect of the extract was also statistically significant (p < 0.01 and p < 0.001) in both carrageenan and formalin-induced paw edema in dose dependent manner. Greater edema inhibition was observed by the highest dose (400 mg/kg) in both observations with the respective percentage values of 70.00% and 79.87%, respectively. CONCLUSION: In general, the data obtained from the present study elucidated that the extract possessed a significant analgesic and anti-inflammatory activities and recommended for further studies.

Anti-inflammatory and central and peripheral anti-nociceptive activities of α-asarone through the inhibition of TNF-α production, leukocyte recruitment and iNOS expression, and participation of the adenosinergic and opioidergic systems.

Alpha-asarone has been found to possess many pharmacological activities, which can improve cognitive function and exert anti-oxidant, anxiolytic, anti-epileptic and protective effects against endothelial cell injury. The anti-inflammatory activity of α-asarone was evaluated using lipopolysaccharide (LPS)-induced paw oedema. Moreover, leukocyte migration, inducible nitric oxide synthase (iNOS) expression and tumour necrosis factor-alpha (TNF-α) levels were quantified in footpads. Formalin and LPS-induced thermal hyperalgesia models were generated using adenosinergic, opioidergic, serotonergic and muscarinic receptor antagonists. The effects on motor coordination were evaluated by means of the rota-rod test. Oral treatment (p.o.) with α-asarone (3 mg/kg) significantly inhibited paw oedema by 62.12 and 72.22%, 2 and 4 h post LPS injection, respectively. Alpha-asarone (3 mg/kg, p.o.) attenuated the inflammatory infiltrate 1, 3 and 6 h after LPS injection. Furthermore, α-asarone (3 mg/kg, p.o.) suppressed iNOS expression and TNF-α production, 6 and 1 h after inflammatory stimulus, respectively. Alpha-asarone (3, 10 and 30 mg/kg, p.o.) inhibited both phases of formalin-induced licking. In the hot-plate test, α-asarone (10 and 30 mg/kg, p.o.) increased the latency to response 3 and 5 h post LPS stimulus. Caffeine and naloxone abolished the central anti-nociceptive effect of α-asarone (neurogenic phase of formalin and hot plate tests), suggesting the participation of the adenosinergic and opioidergic systems. Furthermore, naloxone reversed the peripheral activity of α-asarone (inflammatory phase of formalin test), indicating the possible involvement of the opioidergic pathway. In the rota-rod test, α-asarone did not change motor coordination. These findings suggest that α-asarone has anti-inflammatory, peripheral and central anti-nociceptive effects and could represent a promising agent for future research.

Report on the CCT Supplementary comparison S2 on thermal conductivity measurements of insulating materials by guarded hot plate.

Seven National Metrology Institutes (NMIs) from France, United States, United Kingdom, Russia, Mexico, China and Germany participated in an inter-laboratory comparison on thermal conductivity measurements by the Guarded Hot Plate method. This action was part of a series of supplementary inter-laboratory comparisons (including infrared spectral emittance and thermal diffusivity) sponsored by the Consultative Committee on Thermometry (CCT) Task Group on Thermophysical Quantities (TG-ThQ). The objective of this collaborative work was to strengthen the consistency of thermal conductivity measurements carried out worldwide on low conductive materials. Measurements were conducted successively by all participants on the same sets of specimens of insulating materials (mineral wool and expanded polystyrene) at temperatures ranging from 10 °C to 40 °C, according to the International Standard ISO 8302. This protocol aimed to minimize issues of material variability by circulating the same pairs of specimens among the laboratories following the strict format of a round-robin test program. More than 120 data points (combinations of material, thickness and temperature) were compared. 92 % of the data points were in agreement, with differences to weighted mean values less than the expanded uncertainties calculated from the individual NMI uncertainties and uncertainties related to the comparison process.

Antinociceptive activity of Thyme (Thymus vulgaris L. ) and interactions with neurotropics and analgesics

The plant world represents an important source of potential therapeutic agents, but concomitant administration of herbal and conventional medications may result in interactions with subsequent beneficial or adverse effects. This study was designed to examine the analgesic effect of thyme tincture and thyme syrup, two commonly used thyme formulations, and their interactions with codeine, paracetamol, pentobarbital and diazepam in mice. The identification and quantification of thymol and carvacrol were carried out by GC/MS and GC/FID. The analgesic activity was studied using a hot plate method. Effects of thyme syrup on diazepam-induced motor coordination impairment in rotarod test and on pentobarbital-induced sleeping time were also determined. Thymol (175.3 µg/mL and 9.73 µg/mL) and carvacrol (10.54 µg/mL and 0.55 µg/mL) concentrations were measured in tincture and syrup, respectively. Thyme syrup and tincture exhibited effective analgesic activity in the hot plate pain model. Pretreatment with thyme formulations reduced analgesic activity of codeine, and potentiated the analgesic activity of paracetamol. Co-administration of thyme formulations has led to potentiation of diazepam and pentobarbital depressive central nervous system effects. Thyme formulations interacted with tested conventional drugs, probably through interference with their metabolic pathways and succeeding altered concentrations and pharmacological effects.

Antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb usually grows as a weed in rice fields and is mainly distributed in tropical or sub-tropical countries of south and south-east Asia, central America, northern Australia and west Africa. The plant has been traditionally used to treat fever as a form of poultice. AIM OF THE STUDY: The present study aimed to investigate antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model. MATERIALS AND METHODS: Antipyretic effect of Fimbristylis miliacea was examined using Baker's yeast induced hyperthermia test. Anti-nociceptive effect was investigated using acetic acid induced writhing test, formalin induced hind paw licking test and hot plate test. RESULTS: The extract at concentration of 400 mg/kg produced significant reduction in body temperature after 0.5 h of administration (4.12 °F, p ≤ 0.001) and continued to decrease (after 4 h, 5.92 °F, p ≤ 0.001). Extracts at 100 mg/kg and 200 mg/kg decreased the temperature by about 2.77 °F (from 99.47 °F to 96.7 °F) and 5.58 °F (98.2 °F-92.62 °F) respectively after 4 h whereas paracetamol dropped by about 7.2 °F (p ≤ 0.001). The extract showed significant decrease in number of writhes at all concentrations. Highest effect was found at 200 mg/kg having 35.7 writhes (p ≤ 0.001), much lower than control (89.2); standard drug diclofenac showed 23.2 writhes. Percent inhibition of writhing were 54.26 and 73.99 for 200 mg/kg and diclofenac respectively. The result of hind paw licking test also corroborated writhing test. Significant reduction in percent inhibition of licking was observed mainly in late phase. Percent inhibition of licking were 93.77 and 51.55 for 400 mg/kg extract and diclofenac respectively. In hot plate test, extract at 400 mg/kg showed significant increase in latency from 10.77 s to 13.59 s (p ≤ 0.05). Extract at this dose after 2 h demonstrated greater percent maximal effect (43.26%) compared to ketorolac (40.19%). CONCLUSION: The experiment confirmed the traditional use of F. miliacea in the treatment of fever with possible anti-nociceptive effects.

Assessment of the antinociceptive and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea.

Context: Since there is still a great need to search for plant species with antinociceptive and anti-inflammatory activities, Diploptropis purpurea (Rich.) Amshoff (Fabaceae) is studied for the first time. Objective: This evaluates the analgesic and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea (MEDP). Material and methods: The anti-inflammatory and analgesic effects of MEDP of D. purpurea were evaluated in vivo. The antinociceptive activity was assessed in CD1 male mice were treated by oral gavage with 500 mg/kg of MEDP 30 min before submitting to acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Paws oedema induced by carrageenan, histamine or serotonin were performed in male Sprague-Dawley rats to determinate the anti-inflammatory activity. Results: Oral administration of MEDP produced significant antinociceptive effects on the inflammatory phase in the formalin test [12.0 s versus 72.5 s in carboxymethyl cellulose (CMC) control group]. MEDP produced an analgesic effect in the hot-plate model, although the effect was modest compared to tramadol (40 and 60%, respectively). The oral administration of MEDP in a dose of 500 mg/kg showed maximum inhibition (75.1%) after 0.5 h in carrageenan-induced oedema, but it did not modify histamine or serotonin-induced oedemas. Discussion and conclusion: In the peripheral nociception model, acetic acid-induced abdominal writhing, the MEDP did not show a protective effect, but its analgesic effects were evident in the inflammatory phase of the formalin test and in the hot-plate model. These results show that the anti-inflammatory effect was accompanied by a reduction in the perception of painful stimuli.

Anti-nociceptive and anti-inflammatory activities of crude root extract and solvent fractions of Cucumis ficifolius in mice model.

Background: Societies in developing countries use traditional medicine as alternatives for management of pain and inflammation. The plant Cucumis ficifolius has been used in Ethiopia to treat many ailments including inflammation and pain. The objective of this study was to evaluate the antinociceptive and anti-inflammatory activities of the crude root extract and solvent fractions of C. ficifolius. Methods: The analgesic activity of crude extract and solvent fractions of C. ficifolius was evaluated with acetic acid-induced writhing, hot plate, and formalin-induced paw licking tests. The anti-inflammatory effect of crude methanolic root extract and solvent fractions of C. ficifolius was evaluated using carrageenan-induced paw edema. The crude extract was given at 200, 400 and 800 mg/kg. Butanol and aqueous fractions were given at 100 and 200 mg/kg doses. The negative control groups were treated with distilled water (10 mL/kg). Standard drugs used were acetylsalicylic acid (ASA) in acetic acid, formalin tests and carrageenan-induced paw edema and morphine (20 mg/kg) in hot plate test. Results: The crude extract, at its maximum dose, produced comparable analgesic activity (72.5%) to ASA in acetic acid writhing test. In the hot plate test, both the crude extract and solvent fractions exhibited a significant prolongation of nociception reaction time. Formalin test result indicated a significant reduction of mean lick time with maximal protection of 64% (early phase) and 83% (late phase). Aqueous and butanol fractions showed good analgesic activity in the three models. Inflammation was decreased by 69% with butanol (200 mg/kg); 71% (800 mg/kg) of crude extract and by 41% and 56% with the use of aqueous fraction at 100 and 200 mg/kg, respectively (p<0.001). Conclusion: The present study indicates that the crude methanolic root extract, as well as butanol and aqueous solvent fractions, showed anti-nociceptive and anti-inflammatory activities.

Antinociceptive and anti-arthritic effects of aqueous whole plant extract of Trianthema portulacastrum in rodents: Possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Trianthema portulacastrum L. (Aizoaceae) is used in traditional African Medicine for the treatment of various illnesses including dropsy, inflammation and rheumatism. AIM OF THE STUDY: This study was designed to investigate the anti-nociceptive and anti-arthritic properties of the aqueous whole plant extract of Trianthema portulacastrum (AETP), possible mechanisms of action and characterize some of the active constituents. MATERIALS AND METHODS: Antinociceptive activity was evaluated using the acetic acid-induced writhing and hot plate tests in mice. The carrageenan test was used to induce a transient inflammation while arthritis was induced with complete Freund's adjuvant (CFA) in rats. On completion of CFA-induced arthritis macroscopic observations, the rats were euthanized to isolate the spleen, liver and limbs for estimation of oxidative stress and histological analysis. RESULTS: AETP (10, 50, or 250 mg/kg; p.o.) produced significant (p < 0.05) and dose-dependent inhibition (41.10, 50.40, and 67.10%, respectively) of writhing response elicited by acetic acid. Also, increased pain threshold of supraspinally mediated nociceptive behaviour, with peak maximum possible effect (MPE) obtained at 250 mg/kg (22.98%; 30 min post-treatment). However, the pre-treatment of mice with Nitro-L-arginine (L-NNA) or naloxone reversed AETP-induced antinociception. In another experiment, AETP produced time course inhibition of carrageenan-induced paw oedema with peak effect (50.60%) at 250 mg/kg as well as significant reduction in CFA-induced arthritis by 58.56%, on day 27 and arthritic index (26.84%). Similarly, AETP attenuated CFA-induced MDA generation and deficit in antioxidant enzyme activities. Histological analysis of rat joints revealed a reduction in the synovial hyperplasia and mononuclear infiltration induced by CFA in AETP treated groups. CONCLUSION: Findings from this study showed that T. portulacastrum possesses anti-nociceptive action through nitrergic and opioidergic signalling as well as anti-arthritic effect through enhancement of antioxidant defense system and inhibition of release or actions of inflammatory mediators.

Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2.

Opioid peptides and opiate drugs such as morphine, mediate their analgesic effects, but also undesired side effects, mostly through activation of the mu opioid receptor. However, delta- and kappa-opioid receptors can also contribute to the analgesic effects of opioids. Recent findings showed that simultaneous activation of multiple opioid receptors may result in additional analgesia with fewer side effects. Here, we evaluated the pharmacological profile of our formerly developed mixed mu/kappa-opioid receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH2 (C-36) and Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2 (F-81). The ability of these peptides to cross the blood-brain barrier was tested in the parallel artificial membrane permeability (PAMPA) assay. On the basis of the hot-plate test in mice after central and peripheral administration, analog F-81 was selected for the anti-nociceptive and anti-inflammatory activity assessment after peripheral administration.

Studies on analgesic, anti-inflammatory activities of stem and roots of Inula cuspidata C.B Clarke.

The present study was carried out to evaluate analgesic and anti-inflammatory activities in Inula cuspidata stem and root extracts along with heavy metals estimation in stem and root powder. Stem and roots were extracted with chloroform (ICSCE, ICRCE) and methanol (ICSME, ICRME). Acute oral toxicity of all extracts was determined by OECD guidelines 425. Analgesic activity was investigated by using hot plate and acetic acid induced writhing models. Anti-inflammatory activity (acute) of all extracts was evaluated by carrageenan induced paw edema model. In addition, root and stem powder was screened for heavy metals (As, Pb, Cd, Hg) estimation using atomic absorption spectroscopy. In acute toxicity study no mortality was observed when each extract was orally administered with 2.0 g/kg. At the doses (100 and 200 mg/kg) ICRME followed by ICSME showed significant and dose dependent analgesic and anti-inflammatory effects compared with chloroform extracts. The heavy metals concentration in stem and root powders was found to be within the permissible limits as recommended by WHO for herbal raw materials. The findings of the present study validated the folkloric use of Inula cuspidata as analgesic and anti-inflammatory. In addition, the results intimate that heavy metals present in raw material were found to be within the defined limits, and it exhibits that the therapeutic efficacy of plant may not be effected, which can be otherwise possibly effected if the plant sequester high concentration of heavy metals from the polluted environment as well as from the soil rich in pesticides and sewage sludge etc.

Antinociceptive Activity of Methanol Extract of Tabebuia hypoleuca (C. Wright ex Sauvalle) Urb. Stems.

OBJECTIVE: The aim of this study was to evaluate the antinociceptive activity of the methanol extract of Tabebuia hypoleuca stems (THME). MATERIALS AND METHODS: The animals were divided into 5 groups of 8 mice for each test (negative controls, positive controls, and 3 groups treated with THME at doses of 150, 300, and 500 mg/kg, p.o.). The antinociceptive effect of THME was evaluated using the writhing, formalin, tail flick, and hot plate models in mice. RESULTS: In the writhing test, THME (150, 300, and 500 mg/kg) produced significantly (p < 0.001) fewer writhes induced by acetic acid than in the control group. In the formalin test, the licking time for THME at doses of 300 and 500 mg/kg was significantly shorter (p < 0.001) compared to the control group in the first phase of the formalin test, whereas in the second phase only the dose of 500 mg/kg showed an antinociceptive effect. In addition, THME at doses of 300 and 500 mg/kg significantly increased the latency time in the tail flick test (p < 0.05 and p < 0.001, respectively) and in the hot plate test (p < 0.01 and p < 0.001, respectively) compared to the control group. CONCLUSIONS: These results show that THME had antinociceptive activity using several models of nociception, and they suggest that the effect is mediated by the participation of both peripheral and central antinociceptive mechanisms.

Effect of Sodium Valproate and Docosahexaenoic Acid on Pain in Rats.

INTRODUCTION: Analgesics are commonly prescribed medications used to alleviate pain of various aetiologies without affecting the patient's consciousness. They interfere with the transmission of pain signals. A commonly used antiepileptic drug, sodium valproate has been used in various non-epileptic conditions like migraine prophylaxis and in the treatment of bipolar disorder because of the multiple mechanisms by which it acts. Docosahexanoic Acid (DHA), an omega 3 fatty acid, is known to possess analgesic activity. We planned a study to assess the effect of sodium valproate alone and in combination with DHA in rat models of pain. AIM: To evaluate the analgesic activity of sodium valproate and DHA supplementation using various experimental models in albino Wistar rats. MATERIALS AND METHODS: For analgesic activity, A total of 48 adult Wistar albino rats were divided into eight groups of six rats each. Group I was control (distil water 1 ml/kg), Group II received intraperitoneal injection of tramadol (10 mg/kg), Group III, IV, V were injected intraperitoneal sodium valproate 100, 200, 400 mg/kg with distil water respectively and Group VI, VII, VIII were given sodium valproate 100, 200, 400 mg/kg plus DHA 300 mg/kg (intraperitoneal) respectively. Analgesic activity was assessed using hot plate, tail flick and acetic acid writhing models. RESULTS: We found that sodium valproate at higher doses (400 mg/kg) used either alone along with DHA (300 mg/kg) showed statistically significant analgesic activity in comparison to control in various experimental models for assessing pain. CONCLUSION: Combination of sodium valproate along with DHA has shown promising analgesic activity.