Antinociceptive and anti-inflammatory effects of the ethanol extract of Alpinia conchigera rhizomes in various animal models

Alpinia conchigera Griff. (Zingiberaceae), locally known to the Malays as “lengkuas ranting”, is native to Peninsular Malaysia. The Malays traditionally used it to treat infection and rashes, and as a health drink. This study evaluated the analgesic and anti-inflammatory activities of the ethanol extract of A. conchigera rhizomes in mice and rats, respectively. The analgesic activity was elucidated using the acetic acid-induced writhing test, hot plate test, and formalin test, while the anti-inflammatory activity was determined using carrageenan-induced paw edema. The extract (30, 100, and 300?mg/kg) given intraperitoneally (i.p.) exhibited antinociceptive and anti-inflammatory activities in all tests used. The range of percentage of analgesia obtained for all doses of extract in the writhing test was 50–92%, and in the early and late phases of the formalin test was 25–62% and 63–98%, respectively. In addition, naloxone (5?mg/kg) given subcutaneously (s.c.) was found to reverse the extract (300?mg/kg)-induced antinociceptive activity in the writhing, hot plate, and formalin tests. Based on the results obtained, it can be concluded that the ethanol extract of A. conchigera rhizomes possessed a peripheral and central antinociceptive activity that was mediated, in part, via the opioid receptor, as well as anti-inflammatory activity.     

Antinociceptive effects of the extracts of <Emphasis Type="Italic">Xylopia parviflora</Emphasis> bark and its alkaloidal components in experimental animals

In the present study, we attempted to elucidate the antinociceptive activity of Xylopia parviflora bark using the acetic acid-induced writhing test, hot plate test, and formalin test in mice. The MeOH extract (100 and 200 mg/kg, administered intraperitoneally (i.p.)) had an antinociceptive effect demonstrated by its inhibitory effects on writhing number induced by acetic acid. Three alkaloidal fractions exhibited significant antinociceptive effects in three animal models; the chloroform-soluble fraction, including secondary and tertiary alkaloids, exhibited the strongest effect. This result supported its use in folk medicine as an analgesic agent. We tested the main alkaloids of these fractions for their antinociceptive effects to clarify the active components. (+)-Corytuberine (6.3 and 12.5 mg/kg, i.p.) showed very strong activity, had a significant antinociceptive effect in the acetic acid-induced writhing test (with 49.4 and 98.9% reduction of writhes), in the hot plate test, and in the formalin test (with 55.4 and 90.6% inhibition during the first phase, and 73.9 and 99.9% during the second phase, respectively). (+)-Glaucine (12.5 and 25 mg/kg, i.p.) showed strong activity in three animal models, too. The activity of these compounds was also observed following oral administration in the acetic acid-induced writhing test.     

Antinociceptive,anti-inflammatory and antipyretic properties of an aqueous extract of Corchorus capsularis leaves in experimental animal models

The present study was carried out to establish the antinociceptive, anti-inflammatory and antipyretic properties of an aqueous extract of jute plant leaves, Corchorus capsularis L. (Tiliaceae), in experimental animals. The antinociceptive activity was measured using the abdominal constriction, hot plate and formalin tests, while the anti-inflammatory and antipyretic activities were measured using the carrageenan-induced paw edema and brewer’s yeast-induced pyrexia tests, respectively. The extract, obtained after 72 h soaking of the air-dried leaves in distilled water, freeze-drying for 72 h and then prepared in dosages of 11.57, 57.85, and 115.7 mg/kg, was administered subcutaneously (10 ml/kg) 30 min prior to subjection to the above mentioned assays. The extract was found to exhibit significant (antinociceptive, anti-inflammatory and anti-pyretic, activities in a dosage-independent manner. In conclusion, the aqueous extract of C. capsularis possesses antinociceptive and antipyretic activities and supports the previous claim of its traditional use to treat various ailments.     

Antinociceptive,anti-inflammatory,and antipyretic properties of an aqueous extract of <Emphasis Type="Italic">Dicranopteris linearis</Emphasis> leaves in experimental animal models

This study was performed out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of an aqueous extract of Dicranopteris linearis leaves in experimental animals. The antinociceptive activity was measured using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory and antipyretic activities were measured using the carrageenan-induced paw edema and brewer’s yeast-induced pyrexia tests, respectively. The extract, obtained after 72 h soaking of the air-dried leaves in distilled water and then prepared in the doses of 13.2, 66.0, 132.0, and 660.0 mg/kg, was administered subcutaneously 30 min before subjecting the animals to the assays mentioned above. Generally, the extract, at all doses used, was found to have significant (P < 0.05) concentration-independent antinociceptive, anti-inflammatory, and anti-pyretic activity. In conclusion, the aqueous extract of D. linearis has antinociceptive, anti-inflammatory, and antipyretic activity, supporting previous claims of its traditional use by the Malays to treat various ailments, particularly fever.     

Bioassay-guided isolation of anti-inflammatory and antinociceptive compound from Plumbago zeylanica leaf

Plumbago zeylanica Linn. (Plumbaginaceae) is used in the treatment of various inflammatory ailments in traditional medicines. In order to validate these ethnobotanical practices, the anti-inflammatory and antinociceptive activities of various leaf extracts (petroleum ether (60–80°), chloroform, acetone, ethanol, and aqueous) were studied using in vivo experimental models at two dose levels (200 and 400?mg/kg, p.o.). Anti-inflammatory activity was tested using the carrageenan induced rat hind paw edema method while analgesic activity was studied using the hot plate and formalin induced models. Diclofenac (100?mg/ kg) was used as the reference standard in both anti-inflammatory and analgesic models and morphine (10?mg/ kg, i.p.) was used as the reference standard in the formalin induced analgesic model. The acetone extract significantly (p?<?0.01) reduced inflammation in the rats when compared to the control group. As for the analgesia effect, the acetone and petroleum ether extracts significantly (p?<?0.01) decreased the pain stimulus only in the later phase of the formalin test, suggesting that the drug could be peripherally acting. Bioassay-guided fractionation of the acetone extract led to the isolation and identification of plumbagin. Structure elucidation of plumbagin confirmed it as 5-hydroxy-2-methyl-1,4-naphthoquinone, a naphthaquinone derivative, through spectral techniques.     

Antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract in experimental animal models

The antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract were investigated in experimental animal models. The antinociceptive activity was measured using the writhing, hot plate and formalin tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by in vacuo evaporation to dryness, was weighed and prepared by serial dilution in DMSO in the doses of 20, 100 and 200 mg/kg. The extract was administered (s.c.) 30 min prior to subjection to the respective assays. The extract was found to exhibit significant (p < 0.05) antinociceptive and anti-inflammatory activities. As a conclusion, the present study confirmed the traditional claims of using C. capsularis to treat various ailments related to inflammation and pain.     

Antinociceptive and anti-inflammatory effects of the ethyl acetate stem bark extract of Bridelia scleroneura (Euphorbiaceae)

Bridelia scleroneura is a member of the Euphorbiaceae family. In folk medicine in Cameroon, the stem bark of this plant is used for relieving abdominal pain, contortion, arthritis and inflammation. In this study, the antinociceptive and anti-inflammatory activities of the ethyl acetate stem bark extract have been evaluated. The putative analgesic effect of the plant extract was examined in abdominal constriction, hot plate, formalin and on pain using tail immersion mouse models and in carrageenan-induced paw edema in rats. The extract (150–600 mg/kg) exhibited a dose-dependent analgesic effect (46.27–78.97%) in acetic acid-induced abdominal constriction in mice. B. scleroneura extract increased the pain latency of nociceptive response to thermal stimuli at the higher dose of 600 mg/kg. B. scleroneuna induced significant dose-dependent reduction of the nociception in both early and late phases of the formalin test. The extract at the dose of 300 mg/kg, increased significantly, by 63.70% and 52.01% the tail-immersion latency time, 1 and 2 h post-dosing. In the carrageenan test, B. scleroneura (150–600 mg/kg, p.o) had dose-dependent and significant effects at different time intervals. This behaviour was similar to indometacin (10 mg/kg) used as a standard drug. These results show that the ethyl acetate stem bark extract of B. scleroneura possesses peripheral and central analgesic properties as well as anti-inflammatory activity against acute inflammation processes, in support of the folk medicinal use of the plant.     

Antinociceptive and anti-inflammatory activities of Dicranopteris linearis leaves chloroform extract in experimental animals

The present study was carried out to establish the antinociceptive and anti-inflammatory properties of Dicranopteris linearis leaves chloroform extract in experimental animals. The antinociceptive activity was measured using the abdominal constriction, formalin and hot plate tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by evaporation under vacuo (40 degrees C) to dryness, was dissolved in dimethyl sulfoxide to the doses of 20, 100 and 200 mg/kg and administered subcutaneously 30 min prior to subjection to the above mentioned assays. The extract, at all doses used, was found to exhibit significant (p<0.05) antinociceptive activity in a dose-dependent manner. However, the significant (p<0.05) anti-inflammatory activity observed occur in a dose-independent manner. As a conclusion, the chloroform extract of D. linearis possesses antinociceptive and anti-inflammatory activity and thus justify its traditional uses by the Malays to treat various ailments.     

Antinociceptive,antipyretic, and anti-inflammatory activities of <Emphasis Type="Italic">Putranjiva roxburghii</Emphasis> Wall. leaf extract in experimental animals

The effects of the ether extract from the leaves of Putranjiva roxburghii (P. roxburghii) Wall. were assessed on nociceptive responses in mice by using writhing, hot plate, and formalin tests and the antipyretic activity was determined in yeast-induced fever in rats. Anti-inflammatory activities were also investigated using carrageenin-induced paw edema in rats and croton oil-induced ear and anus edemas. The ether extract (100, 200, and 400 mg/kg, p.o.) of P. roxburghii dose-dependently produced analgesic activity in acetic acid-induced writhing in mice. The extract had no significant effect in the hot plate test in mice. At the dose of 400 mg/kg, the extract significantly suppressed the licking activity in the late phase of the formalin test in mice and decreased fever induced by yeast in rats. The extract exhibited moderate inhibitory activity of inflammation in carrageenin-induced paw edema in rats. The extract inhibited croton oil-induced ear edema in a dose-dependent manner (1.25, 2.5, and 5.0 mg/ear) in mice. The extract decreased anus edema induced by croton oil at the high dose of 800 mg/kg in rats. The results indicated that the ether extract of P. roxburghii leaves possesses analgesic, antipyretic, and anti-inflammatory activities.     

Pereskia aculeata: A plant food with antinociceptive activity

Abstract

Context: Pereskia aculeata Miller (Cactaceae) is a cactus distributed from south to northeast of Brazil, where its leaves are commonly used as a vegetable, in skin wound healing, and to treat inflammation.

Objectives: The objective of this study was to perform the chemical characterization and to evaluate the antinociceptive activity of the hydromethanolic fraction obtained from the methanol extract of P. aculeata leaves.

Materials and methods: Chemical characterization was performed by UPLC–MS analysis. The antinociceptive activity was evaluated by the acetic acid-induced writhing, formalin, and tail-flick tests in mice, administering the single oral doses of 100, 200, and 300?mg/kg 1?h before each test.

Results: Tryptamine, abrine, mescaline, hordenine, petunidin, di-tert-butylphenol isomers, and quercetin were identified. The antinociceptive activity was inversely proportional to the administered doses in the acetic acid test, as the dose of 100?mg/kg reduced by 78% the number of writhings, while the doses of 200 and 300?mg/kg reduced by 64% and 41%, respectively. In the formalin test, the dose of 300?mg/kg inhibited by 50% and 86% the licking paw time in the first and second phases, respectively, while the doses of 200?mg/kg (45% and 62%, respectively) and 100?mg/kg (15% and 48%, respectively) were less effective. The sample did not respond to the tail-flick test. Those results suggested a peripheral and central antinociception devoid of an opioid effect.

Conclusion: Pereskia aculeata not only is a plant food with high nutritional value but also presents analgesic potential. It is the first time that this bioactivity is reported for this species.     

Antinociceptive activity of steroid alkaloids isolated from Solanum trilobatum Linn.

Solasodine (1) was isolated for the first time from the roots of Solanum trilobatum Linn., a member of the Solanaceae, and assessed for its presumed antinociceptive activity using several experimental murine models, viz. the writhing, formalin, and hot plate tests. When used at doses of 2, 4, and 8 mg/kg, this steroidal alkaloid caused a significant and dose-dependent decrease in the nociception induced by an intraperitoneal injection of acetic acid (p < 0.001). It also led to a significant reduction of the painful sensation caused by formalin in both phases of the formalin test (p < 0.001). Furthermore, the alkaloid produced a significant increase in the reaction time in the hot plate test (p < 0.001). These results suggest that solasodine elicited antinociceptive activity through both central and peripheral mechanisms.     

Analgesic Activity of Caesalpinia bonducella Flower Extract

Caesalpinia bonducella Fleming (Leguminosae) flower extract (CBFE) was administered orally (30, 100, and 300 mg/kg) and tested for analgesic and antipyretic activities in adult mice and rats. Analgesic activity was investigated in capsaicin-induced pain, formalin-induced pain, acetic acid-induced writhing test, hot plate test, and tail flick test. Antipyretic activity was tested in Brewer's yeast-induced pyrexia in rats. The extract was found to have significant antinociceptive effect in inflammatory phase of formalin-induced pain and acetic acid-induced parietal pain.     

Antinociceptive and anti-inflammatory activities of the aqueous extract of <Emphasis Type="Italic">Kaempferia galanga</Emphasis> leaves in animal models

This study was performed to determine the antinociceptive and anti-inflammatory activities of aqueous extract of Kaempferia galanga leaves using various animal models. The extract, in the doses of 30, 100, and 300 mg/kg, was prepared by soaking (1:10; w/v) the air-dried powdered leaves (40 g) in distilled water (dH₂O) for 72 h and administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot-plate and formalin tests, with activity observed in all tests occurring in a dose-dependent manner. Furthermore, the antinociceptive activity of K. galanga extract was significantly (P < 0.05) reversed when prechallenged with 10 mg/kg naloxone. The extract also produced a significantly (P < 0.05) dose-dependent anti-inflammatory activity when assessed using the carrageenan-induced paw-edema test. In conclusion, this study demonstrated that K. galanga leaves possessed antinociceptive and anti-inflammatory activities and thus supports the Malay’s traditional uses of the plant for treatments of mouth ulcer, headache, sore throat, etc.     

Central components in the antinociceptive activity of dipyrone in mice

Dipyrone is classified as a nonsteroidal anti-inflammatory drug. It has analgesic, antipyretic and anti-inflammatory properties and exerts its analgesic effect via both peripheral and central action. Dipyrone at the dose of 250 and 500 mg/kg showed dose-dependent antinociceptive activity in the hot plate, tail flick tests to radiant heat and tail clip test and the writhing test induced by acetic acid in mice. The antinociceptive effects of dipyrone (500 mg/kg) were antagonized by naloxone (1, 2, 5 mg/kg) in the tail flick test to radiant heat and tail clip test and hot plate tests but not in the writhing test. Cyproheptadine (100 g/kg) decreased the antinociceptive effect of dipyrone. There was an increase in the antinociceptive effects of dipyrone (500 mg/kg) when combined with buspiron (0.5 mg/kg) in the tail flick test to radiant heat and tail clip test. The results provide evidence for a central antinociceptive effect of dipyrone antagonized by naloxone which suggests that its activity may also involve the serotoninergic system.     

Phytochemical Screening and Evaluation of Analgesic Activity of Oroxylum indicum

We aimed to study phytochemical screening and analgesic activity of ethanol extract of Oroxylum indicum. The dried powder of the barks of the plant was extracted with 95% ethanol and was subjected to various phytochemical tests to ascertain the principle constituents contained in the extract. The result revealed the presence of alkaloids, flavonoids, tannins, glycosides in the ethanol extract of Oroxylum indicum. The extract was screened for analgesic activity by using hot plate, acetic acid-induced writhing and formalin test. The ethanol extract of the plant at two different doses (250 and 500 mg/kg) showed significant (P<0.05) analgesic effect in all test methods (hot plate, acetic acid-induced writhing and formalin). The analgesic activity was compared with a standard drug (ketorolac at 10 mg/kg). Based on the present findings and previous literature review it can be concluded that flavonoids and tannins might be responsible for the analgesic activity. We suggest that ethanol extract of Oroxylum indicum might have potential chemical constituents that could be used in the future for the development of novel analgesic agent.     

The stem bark extracts of Cenostigma macrophyllum attenuates tactile allodynia in streptozotocin-induced diabetic rats

Abstract

Context. Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae- Caesalpinioideae) is popularly known as “caneleiro”. Previous studies showed antioxidant action and analgesic effects of the ethanol extract from the leaves of C. macrophyllum. The phytochemical evaluation of the stem bark revealed the presence of antinociceptive compounds.

Objective: To investigate the antinociceptive actions of the ethanol extract and ethyl acetate fraction from C. macrophyllum stem bark in streptozotocin (STZ)-induced diabetic rats and the involvement of opioid and nitrergic mechanisms.

Materials and methods: STZ-rats received the ethanol extract (E.EtOH 200 and 300?mg/kg, p.o.) during 5 weeks. In acute experiments, untreated diabetic rats were treated with the ethyl acetate fraction (F.EtOAc 250 and 500?mg/kg, p.o.), on the 28th day of diabetes induction when the opioid and nitrergic mechanisms were investigated. The mechanical nociceptive threshold (MNT) was determined by application of von Frey filaments.

Results: Data show that STZ-induced diabetic rats developed a significant tactile allodynia during 5 weeks. Diabetic rats that received E.EtOH (200 and 300?mg/kg) and F.EtOAc (250 and 500?mg/kg) had a pain threshold higher than those in the STZ-vehicle group. F.EtOAc effects were inhibited by pretreatment with naloxone and were not influenced by .-arginine.

Discussion and conclusion: The results suggest that the ethanol extract and ethyl acetate fraction of C. macrophyllum presented antinociceptive activity. Thus, F.EtOAc may be exerting its effect by affecting the opioid system, but nitrergic mechanisms are not detectable. The observed activity may be due to its gallic acid, lupeol and bergenin content.     

Anti-inflammatory,analgesic, and antioxidant activities of Pisonia aculeata: Folk medicinal use to scientific approach

Context: Pisonia aculeata leaves (Nyctagenaceae), a Folk medicinal plant used in the treatment of several inflammation, pain, and oxidative stress associated diseases.

Objective: To evaluate anti-inflammatory, analgesic, and antioxidant potential of crude methanol extract of P. aculeata leaves (MEPA).

Materials and methods: Analgesic and anti-inflammatory activities of MEPA (250 and 500?mg/kg) were evaluated using writhing, formalin, hot plate, tail flick, carrageenan-induced paw edema test, and membrane stabilizing activity. Free radical scavenging activity, total phenolic and flavonoid contents of MEPA were also determined using standard methods.

Results: Oral administration of MEPA showed significant (p < 0.001) inhibition of paw edema, pronounced at 4?h and 5?h after carrageenan injection, and at 200 µg/mL exerts 77.67 and 38.51% protective effect against hypotonic solution and heat induced hemolysis, respectively. MEPA (250 and 500?mg/kg) produced 35.21 and 79.14% inhibition of acetic acid-induced writhing. Furthermore, MEPA (500?mg/kg) inhibited 49.19% early and 73.14% late phase of formalin-induced hypernociception. In contrast, a lower dose of MEPA did not prevent hot plate induced nociception, while in the tail immersion method, pronounced analgesic activity was observed between 1 and 4?h postdosing. The extract possesses significant in vitro antioxidant activity and a lipid peroxidation inhibition effect. Total phenolic and total flavonoid content in MEPA were 87.99?±?0.87?mg GAE/g and 58.98?±?0.01?mg QE/g, respectively.

Discussion and conclusion: Our findings confirmed the analgesic, anti-inflammatory and antioxidant activities of Pisonia aculeata leaves. Contents of flavonoids and phenolic compounds in extract could be correlated with its observed biological activities.     

Antinociceptive and anti-inflammatory effects of isolated fractions from Apium graveolens seeds in mice

The antinociceptive and anti-inflammatory effects of the aqueous and hexane extracts obtained from Apium graveolens L. (Apiaceae) seeds were evaluated. Formalin and xylene-induced ear edema tests were used in mice. The fractions were administered intraperitoneally at doses of 100-500?mg/kg body weight (BW). Both extracts with the xylene-induced ear edema test showed significant anti-inflammatory activity at all doses as compared with control. Only the hexane fraction reduced the nociception produced by formalin solution in the first phase (0-5?min) at 300, 400, and 500?mg/kg BW, and in the second phase (20-30?min) at 500?mg/kg BW. It is concluded that the hexane fraction has major contribution to the overall antinociceptive activity. Both fractions showed remarkable anti-inflammatory effect which supported the traditional use of Apium graveolens in diseases associated with inflammation.     

Antinociceptive Properties of the Hydroalcoholic Extract and the Flavonoid Rutin Obtained from Polygala paniculata L. in Mice

Abstract: The present study examined the antinociceptive effects of a hydroalcoholic extract of Polygala paniculata in chemical and thermal behavioural models of pain in mice. The antinociceptive effects of hydroalcoholic extract was evaluated in chemical (acetic‐acid, formalin, capsaicin, cinnamaldehyde and glutamate tests) and thermal (tail‐flick and hot‐plate test) models of pain or by biting behaviour following intratecal administration of both ionotropic and metabotropic agonists of excitatory amino acids receptors glutamate and cytokines such as interleukin‐1β (IL‐1β) and tumour necrosis factor‐α (TNF‐α) in mice. When given orally, hydroalcoholic extract (0.001–10 mg/kg), produced potent and dose‐dependent inhibition of acetic acid‐induced visceral pain. In the formalin test, the hydroalcoholic extract (0.0001–0.1 mg/kg orally) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin‐induced licking. However, it was more potent and efficacious in relation to the late phase of the formalin test. The capsaicin‐induced nociception was also reduced at a dose of only 1.0 mg/kg orally. The hydroalcoholic extract significantly reduced the cinnamaldehyde‐induced nociception at doses of 0.01, 0.1 and 1.0 mg/kg orally. Moreover, the hydroalcoholic extract (0.001–1.0 mg/kg orally) caused significant and dose‐dependent inhibition of glutamate‐induced pain. However, only rutin, but not phebalosin or aurapten, isolated from P. paniculata, administered intraperitoneally to mice, produced dose‐related inhibition of glutamate‐induced pain. Furthermore, the hydroalcoholic extract (0.1–100 mg/kg orally) had no effect in the tail‐flick test. On the other hand, the hydroalcoholic extract caused a significant increase in the latency to response at a dose of 10 mg/kg orally, in the hot‐plate test. The hydroalcoholic extract (0.1 mg/kg orally) antinociception, in the glutamate test, was neither affected by intraperitoenal treatment of animals with l ‐arginine (precursor of nitric oxide, 600 mg/kg) and naloxone (opioid receptor antagonist, 1 mg/kg.) nor associated with non‐specific effects such as muscle relaxation or sedation. In addition, oral administration of hydroalcoholic extract produced a great inhibition of the pain‐related behaviours induced by intrathecal injection of glutamate, N‐methyl‐d ‐aspartate (NMDA), IL‐1β and TNF‐α, but not by α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionic acid (AMPA), kainate or trans‐1‐amino‐1.3‐cyclopentanediocarboxylic acid (trans‐ACPD). Together, our results suggest that inhibition of glutamatergic ionotropic receptors, may account for the antinociceptive action reported for the hydroalcoholic extract from P. paniculata in models of chemical pain used in this study.