Evaluation of anti-inflammatory activity of chloroform extract of Bryonia laciniosa in experimental animal models

The anti-inflammatory effect of the leaves of Bryonia laciniosa was evaluated using carrageenan, dextran, histamine, serotonin induced rat paw oedema and cotton pellet induced granuloma (chronic) models in rats. In mice, carrageenan peritonitis test was performed for the extract by oral administration. The chloroform extract of Bryonia laciniosa (CEBL) exhibited significant anti-inflammatory effect at the dose 50, 100 and 200 mg/kg. Maximum inhibition (52.4%) was noted at the dose of 200 mg/kg after 3 h of drug treatment in carrageenan induced paw oedema, whereas the indomethacin (standard drug) produced 62.1% of inhibition. The extract exhibited significant anti-inflammatory activity in dextran induced paw oedema in a dose dependent manner. The extract also exhibited significant inhibition on the hind paw oedema in rats caused by histamine and serotonin respectively. In the chronic model (cotton pellet induced granuloma) the CEBL (200 mg/kg) and standard drug showed decreased formation of granuloma tissue by 50.1 and 57.3% (p<0.001) respectively. The extract also inhibited peritoneal leukocyte migration in mice. Thus, the present study revealed that the chloroform extract of Bryonia laciniosa exhibited significant anti-inflammatory activity in the tested models.     

Study of anti-inflammatory and antinociceptive activity of hydroalcoholic extract of Schima wallichii bark

Hydroalcoholic extract of Schima wallichii Choisy. (Ternstroemiaceae) bark (HESW) was investigated for its anti-inflammatory, antinociceptive, and antipyretic activities. The anti-inflammatory effects of the HESW were assayed by using carrageenan and dextran (acute model) induced paw edema and cotton pellet granuloma assay (chronic model) in experimental rats. Oral administration of HESW at the doses of 150 and 300?mg/kg caused dose-dependent inhibition of carrageenan and dextran induced inflammation. HESW at the doses of 150 and 300?mg/kg caused significant dose-dependent reduction of the granuloma tissue formation in experimental rats. The extract at the oral doses of 50 and 100?mg/kg body weight exhibited significant central and peripheral analgesic activity in acetic acid induced writhing test and hot-plate test respectively in experimental mice. Treatment with HESW at the oral doses of 150 and 300?mg/kg body weight significantly reduced the yeast-provoked elevated body temperature in experimental rats in a dose-dependent manner.     

Evaluation of anti-inflammatory and antinociceptive effects of D-002 (beeswax alcohols)

D-002, a mixture of six higher aliphatic alcohols purified from beeswax, displayed anti-inflammatory effects in carrageenan-induced pleurisy and cotton pellet granuloma in rats. The aim of the present study was to confirm the anti-inflammatory properties of D-002 and to explore its potential analgesic effects. Xylene-induced mouse ear oedema was used to assess the anti-inflammatory effect, acetic acid-induced writhing and hot plate responses for the analgesic activity, and the open field and horizontal rotarod tests for motor performance. For anti-inflammatory tests, mice were randomised into a negative vehicle control and five xylene-treated groups: the vehicle, D-002 (25, 50 and 200 mg/kg) and indomethacin 1 mg/kg (reference drug). Treatments were given for 15 days. Effects on oedema formation and myeloperoxidase (MPO) activity were tested. For analgesia and motor performance tests, mice were randomised into a vehicle control and D-002-treated groups (25, 50 and 200 mg/kg). Two sets of experiments were done, which included acute and repeat (15 days) dosing. D-002 (25, 50 and 200 mg/kg) significantly decreased xylene-induced ear oedema (44.7, 60.8 and 76.4%, respectively) and the increase of MPO activity induced by xylene (38.0, 47.0 and 57.0%, respectively), while indomethacin significantly inhibited xylene-induced oedema (59.9%) and MPO activity (57.5%). Single and repeat doses of D-002 (25, 50 and 200 mg/kg) decreased the acetic acid-induced writhing responses by 21.2, 28.2 and 40.1%, for the single doses; 25.2, 35.1 and 43.2%, respectively, for the repeat doses, but did not affect the hot plate, open field and rotarod behaviours. Aspirin 100 mg/kg significantly decreased acetic acid-induced abdominal constrictions and morphine (5 mg/kg) significantly increased the latency of the hot plate response. This study confirmed the anti-inflammatory effects of D-002 and demonstrated its analgesic effects on the acetic acid-induced writhing, but not on the hot plate response, which suggests that the antinociceptive effects of D-002 could be related to its anti-inflammatory activity.     

Evaluation of analgesic and anti-inflammatory activities of Nectandra megapotamica (Lauraceae) in mice and rats

The bioactivity-guided phytochemical investigation of the crude hydralcoholic extract of Nectandra megapotamica was carried out using the abdominal constriction test in mice, which led to the isolation of three active compounds: alpha-asarone (1), galgravin (2) and veraguensin (3). The crude extract (EBCA, 300 mg kg(-1)) and isolated compounds 1,2, and 3, at different doses, were evaluated using the acetic acid-induced abdominal constriction test in mice, carrageenan-induced paw oedema in rats, and hot plate tests in rats. The EBCA showed a significant effect in the abdominal constriction and hot plate tests, but did not show activity in the rat paw oedema assay. All isolated compounds displayed activity in the abdominal constriction test, but only compound 1 was active in the hot plate test. Compounds 2 and 3 displayed activity in the anti-inflammatory assay. It was suggested that the analgesic effects obtained for EBCA could be due mainly to the presence of its major compound, alpha-asarone (1).     

Studies on the anti-inflammatory and anti-nociceptive effects of melatonin in the rat.

The present study aimed to evaluate the anti-inflammatory and anti-nociceptive effects of melatonin in the rat. Acute inflammation was induced by sub-plantar injection of carrageenan (1%) in the rat hind paw. The rats received vehicle or drug 30 min before carrageenan administration and were evaluated for paw oedema at 1, 2, 3, and 4 h post-carrageenan. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Nociception was tested by determining vocalization following electrical stimulation of the tail. Given intraperitoneally (i.p.) 30 min before carrageenan, melatonin caused significant and a dose-dependent reduction of hind paw swelling induced by carrageenan. At doses of 0.5 and 1 mg kg(-1), melatonin inhibited the carrageenan-induced oedema by 20.5 and 29.6% versus control values at 4 h post-carrageenan, respectively. Melatonin (0.5 and 1 mg kg(-1), i.p.) 30 min beforehand displayed anti-nociceptive effect in the electric stimulation of the rat tail test, increasing nociceptive thresholds to electrically-induced pain at 4 h post-treatment by 29.6 and 39.5%, respectively. Melatonin given simultaneously with the non-selective COX-1 and COX-2 inhibitor indomethacin (5 mg kg(-1), i.p.) 30 min prior to carrageenan, enhanced the anti-inflammatory effect of the latter in the carrageenan-induced paw oedema model by 23%. Melatonin (0.5 mg kg(-1), i.p.) increased the anti-nociceptive effect of indomethacin (5 mg kg(-1), i.p.). Meanwhile, the anti-inflammatory and anti-nociceptive effect of the highly selective COX-2 inhibitor rofecoxib (2.25 mg kg(-1), i.p.) was only slightly increased by melatonin administration at 0.5 mg kg(-1). Melatonin enhanced the anti-inflammatory effect of cysteamine (300 mg kg(-1), s.c.) in the carrageenan-induced paw oedema. Melatonin (20 and 40 microg per paw) given prior to carrageenan into the rat hind paw was devoid of anti-inflammatory effect. These results indicate that melatonin possesses anti-inflammatory and anti-nociceptive properties in the rat and enhance those of indomethacin. This effect is likely to be centrally mediated.     

Evaluation of the anti-inflammatory and anti-nociceptive effects of different antidepressants in the rat.

The present study was designed to compare the anti-inflammatory and anti-nociceptive effects of different classes of antidepressant drugs on the carrageenan paw oedema and tail-electric stimulation assays in the rat. Drugs were intraperitoneally administered 30 min prior to carrageenan or nociceptive testing. The non-selective noradrenaline (NA) and serotonin (5-HT) reuptake inhibitors imipramine, amitriptyline and clomipramine displayed anti-inflammatory activity in the carrageenan model of paw inflammation. The maximal degree of oedema inhibitions seen with these agents were 28.8, 41.5 and 46.8% for 5, 10 and 20 mg kg(-1) amitriptyline, 26.2, 38.2 and 51.4% for 3.75, 7.5 and 15 mg kg(-1) imipramine and 51.2 and 54.1% for 16 and 32 mg kg(-1) clomipramine, respectively. The heterocyclic agent trazodone significantly inhibited paw oedema by 46 and 41% at 1 and 2h after dosing at the highest dose (40 mg kg(-1)) examined. Fluoxetine, a selective 5-HT reuptake inhibitor (SSRI) caused dose-related reduction of paw oedema, with 20.7% inhibition at the dose of 10 mg kg(-1). In contrast, sertraline, another SSRI caused dose-dependent enhancement of paw oedema. All antidepressant drugs in the study showed anti-nociceptive properties in the tail-electric stimulation assay with amitriptyline and trazodone being the most effective in this respect. Taken together, data in the present study confirm anti-inflammatory and anti-nociceptive effect for some antidepressant drugs and indicate that SSRIs differently affects inflammation.     

Analgesic and anti-inflammatory effect of aqueous extract of the stem bark of <Emphasis Type="Italic">Allanblackia gabonensis</Emphasis> (Guttiferae)

Allanblackia gabonensis (Guttiferae) is a plant used in the African traditional medicine as remedies against pain, rheumatism, inflammations. In the present work, the analgesic effect of aqueous extract has been evaluated using acetic acid, formalin, hot-plate test, tail immersion and paw-pressure test. The anti-inflammatory effect of this extract was also investigated on carrageenan, histamine or serotonin induced by paw oedema. Aqueous extract of stem bark of A. gabonensis administrated p.o. showed significant activity against paw oedema induced by carrageenan, with a maximum percentage of inhibition reaching the 74.01% at the preventive test at a dose of 200 mg/kg. A. gabonensis exhibited a significant reduction of paw oedema induced by both histamine and serotonin with a maximal inhibition of 56.94% (200 mg/kg) and 40.83% (100 mg/kg), respectively. It showed significant protective effects against chemical stimuli (acetic acid and formalin) in the mouse. Administered orally at the doses of 100–400 mg/kg, exhibited protective effect of at least 69.78% on the pain induced by acetic acid and also reduced first (67.18% at 200 mg/kg) and second (83.87% at 400 mg/kg) phase of pain-induced par formalin. It also produced a significant increase of the threshold of sensitivity to pressure and hot plate-induced pain in the rats. These results suggest a peripheral and central analgesic activities as well as an anti-inflammatory effect of the stem bark of A. gabonensis.     

Antinociceptive and anti-inflammatory properties of the hydroalcoholic extract of stems from Equisetum arvense L. in mice.

In this study, antinociceptive and anti-inflammatory effects of hydroalcoholic extract of stem from Equisetum arvense in mice were evaluated. The extract (10, 25, 50 and 100mgkg(-1), i.p.), reduced the writhing induced by acetic acid in 49, 57, 93 and 98%, respectively. In the formalin test, 50 and 100mgkg(-1) (i.p.) extract, reduced in 80 and 95% the licking activity in the first phase, but in the second phase only the latter dose diminished the licking time (35%). In both phases, naloxone failed to revert the analgesic effect of the extract. In the hot-plate test, the extract at 100 and 200mgkg(-1) does not change the latency to licking or jumping. In the carrageenan-induced paw oedema, the extract at 50mgkg(-1), reduced the paw oedema 2h (25%) and 4h (30%) after carrageenan administration. The dose of 100mgkg(-1) caused reduction of the paw oedema (29%) only 4h after carrageenan administration. These results indicate that this extract exhibits an antinociceptive effect in chemical models of nociception which is not related to the opioid system, as well as anti-inflammatory properties.     

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.     

Evaluation of the anti-inflammatory, anti-nociceptive and gastric effects of Ginkgo biloba in the rat.

Ginkgo biloba extract (GbE) was assessed in models of acute inflammation induced by carrageenan, formalin or capsaicin in the rat, in models of nociceptive pain, such as hot-plate (55 degrees C) latency, tail-electric stimulation assay and capsaicin-induced paw licking and in the model of acute gastric damage induced by indomethacin. The agent showed marked anti-inflammatory activity in the carrageenan model of paw oedema. When given subcutaneously (s.c.) (25 and 50 mg kg(-1)) 30 min before challenge, GbE inhibited paw oedema with a maximal effect of 43.7 and 56.9%, respectively, at 2h post-carrageenan. Significant inhibition of oedema was also observed when GbE (50 mg kg(-1), s.c.) was given 30 min after carrageenan challenge. The agent was also active p.o. in acute inflammation caused by carrageenan. The administration of GbE with indomethacin, rofecoxib, celecoxib, dexamethasone or melatonin resulted in an additive effect. GbE (50 mg kg(-1), s.c.) caused significant inhibition of formalin-induced paw oedema, but did not reduce the capsaicin-induced paw oedema. In tests of nociception, GbE (25, 50 or 100 mg kg(-1)) decreased in dose-dependent manner the capsaicin-induced hind paw licking time and was similarly effective in the hot-plate assay of nociception. In contrast, when assessed in the tail-electric stimulation test, GbE was only effective in the highest dose (100 mg kg(-1)). In pylorus-ligated rats, GbE (25 or 50 mg kg(-1)) increased gastric acid secretion, but reduced gastric mucosal damage caused by IND. Results suggest that GbE may be of clinical value as an anti-inflammatory and analgesic drug alone or in conjunction with NSAIDs.     

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.     

Anti-inflammatory, analgesic and antipyretic activity of aqueous extract of fresh leaves of Coccinia indica

This study was aimed to evaluate both post- and pre-treatment anti-inflammatory activities of the aqueous extract of fresh leaves of Coccinia indica in rats using the carrageenan-induced paw oedema method at various dose levels. Analgesic and antipyretic properties were evaluated using tail flick model and yeast-induced hyperpyrexia, respectively. Ceiling effect of the extract was observed at 50 mg/kg in pre-treatment carrageenan test. In post-treatment studies, a dose-dependent anti-inflammatory effect was observed in the dose range of 25–300 mg/kg. The effect was equivalent to diclofenac (20 mg/kg) at 50 mg/kg but it was significantly pronounced at higher doses. Effectiveness of extract in the early phase of inflammation suggests the inhibition of histamine and serotonin release. The extract produced marked analgesic activity comparable to morphine at 300 mg/kg, which suggests the involvement of central mechanisms. A significant reduction in hyperpyrexia in rats was also produced by all doses of extract with maximum effect at 300 mg/kg comparable to paracetamol. In conclusion, this study has established the anti-inflammatory activity, analgesic and antipyretic activity of C. indica and, thus, justifies the ethnic uses of the plant.     

Antinociceptive and antiinflammatory activities of Artemisia copa extracts.

The aqueous extract from aerial parts of Artemisia copa Phil. (Compositae), was evaluated for antinociceptive activity using writhing, formalin, and hot-plate tests in mice. A dose-related antinociceptive response was obtained in the writhing test at doses of 500 and 1000 mg/kg p.o. (percentage of inhibition 23.3 and 52.70, respectively). The extract also inhibited the second phase of formalin test (38.81%) and this effect was not antagonized by pretreatment with naloxone 5mg/kg i.p. Furthermore, no significant effect was obtained in the hot-plate test. Dichloromethane and ethanolic extracts, were analyzed for antiinflammatory activity with the carrageenan-induced paw edema in rats and the ear edema induced by 12-O-tetradecanoylphorbol-13 acetate (TPA) and arachidonic acid (AA) in mice. Both extracts showed antiinflammatory activity in the TPA (88 and 54%), and the ethanolic extract showed a 37% inhibition in AA test. No effects were seen at doses of 300 mg/kg p.o. and 100 mg/kg i.p. in the carrageenan test. The results obtained indicate that A. copa has analgesic and topical antiinflammatory activities that supports the folk medicinal use of the plant.     

The anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline in the rat.

The present study aimed to evaluate the anti-inflammatory effects of pentoxifylline (PTX), a non-specific phosphodiesterase inhibitor in the rat. Acute inflammation was induced by subplantar injection of carrageenan (1%) in the rat hind paw. Results showed that intraperitoneal (i.p.) administration of PTX (36 or 72 mg kg(-1)) 30 min prior to carrageenan reduced the paw oedema response in dose-dependent manner with a maximal effect of 18.9 and 40.1%, respectively, at 2h post-carrageenan (P<0.001 and <0.001 at respective doses). Theophylline given at equimolar doses (29.9 or 45.8 mg kg(-1), i.p.) did not reduce the oedema response. With higher doses of PTX (144-300 mg kg(-1), i.p.) the anti-oedema effect of the drug was more pronounced, but mainly confined to the first 2h following carrageenan injection and decreasing rapidly thereafter. PTX (72 mg kg(-1), i.p.) given 30 min after carrageenan challenge reduced the oedema response by 24.7 and 26.2% at 1 and 2h after dosing (P<0.05 and <0.05, respectively). PTX (36 or 72 mg kg(-1), i.p.) co-administered with indomethacin (5 mg kg(-1), i.p.) 30 min before carrageenan had little modulatory effect on the anti-oedema effect of indomethacin, but the higher dose of PTX (144 mg kg(-1), i.p.) reduced the anti-inflammatory effect of indomethacin by 24% at 4h post-carrageenan. PTX (72 mg kg(-1), i.p.) enhanced the anti-oedema effect of the selective COX-2 inhibitor celecoxib (33 mg kg(-1), i.p.) by 55.1% at 4h post-carrageenan. In contrast, the higher dose of PTX (144 mg kg(-1), i.p.) reduced the anti-oedema effect of celecoxib by 46.8% at 4h post-carrageenan. PTX (36 or 72 mg kg(-1)) enhanced the anti-oedema effect of dexamethasone (0.1 mg kg(-1)) with maximal effect of 76 and 104.8% at 2h post-carrageenan (P<0.01 and <0.01 for respective doses). PTX (0.6 mg per paw) given with carrageenan into the rat hind paw reduced the oedema response with a maximal effect of 33.4% at 1h following carrageenan. PTX (0.6 mg per paw) given in the contralateral hind paw reduced the carrageenan-induced paw oedema for 1h by 32.2%. Thus, PTX, when given at doses comparable to those used in man for treatment of circulatory disorders displayed anti-inflammatory in vivo and enhanced the anti-inflammatory effect of a selective COX-2 inhibitor or dexamethasone. PTX may have therapeutic potential as anti-inflammatory agent either alone or in combination with non-steroidal anti-inflammatory drugs or with steroids. There is also an intriguing possibility for the use of topical preparations for the management of local inflammatory conditions.     

Anti-inflammatory and immunomodulating properties of a sterol fraction from Sideritis foetens Clem

A sterol fraction composed of campesterol (7.6%), stigmasterol (28.4%) and beta-sitosterol (61.1%) was obtained by activity-guided fractionation of the acetone extract of Sideritis foetens Clem. This sterol fraction showed anti-inflammatory activity in in vivo murine models of inflammation. It decreased carrageenan paw oedema in mice after oral administration of 30 and 60 mg/kg and inhibited mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA) after topical application. Quantitation of the neutrophil specific marker myeloperoxidase (MPO) demonstrated that its topical anti-inflammatory activity was associated with reduction in neutrophil infiltration into inflamed tissues. Non-cytotoxic concentrations of the sterol fraction inhibited leukocyte granular enzyme release (beta-glucuronidase) and superoxide generation. However, it did not shown any significant inhibitory effect on histamine release from mast cells. In vitro modulatory activity towards the classical pathway of the complement system shown by this fraction would correlate with the anti-inflammatory profile shown in vivo.     

Anti-inflammatory and analgesic activities of the ethanolic extracts from Zanthoxylum riedelianum (Rutaceae) leaves and stem bark

We have evaluated the anti-inflammatory and analgesic properties of the leaves (LCE) and stem bark (BCE) crude extracts of Zanthoxylum riedelianum (Rutaceae). Different fractions of the stem bark extract (hexane, BCEH; dichloromethane, BCED; ethyl acetate, BCEE; and lyophilized aqueous residual, BCEW) were also investigated. We studied the effects of the extracts and fractions using the rat paw oedema test induced by carrageenan, dextran, histamine or nystatin; the mouse abdominal constriction test; the mouse hot-plate test (only for LCE and BCE); and the mouse formalin test. Both extracts and all BCE fractions displayed anti-inflammatory activity in the carrageenan-induced oedema model, but not for dextran, histamine or nystatin. Considering the analgesic models, both extracts showed antinociceptive activity, but BCE was more active than LCE in models of central pain. All BCE fractions showed significant inhibition in the abdominal constriction test and in both phases of the formalin test. When BCED was submitted to phytochemical procedures it led to the isolation of six lignans (sesamin, methylpluviatolide, dimethylmatairesinol, piperitol-4(')-O-(gamma),(gamma)-dimethylallyl ether, kaerophyllin and hinokinin), and a triterpene (lupeol). Inhibition of cyclooxygenase and its metabolites may have been involved in the mechanism of action of this plant, considering previous studies reporting the anti-inflammatory and analgesic activity for the identified lignans, as well as anti-inflammatory activity for lupeol.     

Analgesic, antioedematous and antioxidant activity of γ-butyrolactone derivatives in rodents

In this paper, the analgesic, antioedematous, motor-impairing and antioxidant properties of four γ-butyrolactone derivatives (BM113, BM113A, BM138 and BM138A) are described. Pain was induced by thermal (hot-plate test), chemical (writhing test) or mechanical (Randall-Selitto model) stimulation. All in-vivo assays were carried out in mice pretreated intraperitoneally with the test compounds, except for the evaluation of anti-inflammatory and analgesic activities in the carrageenan-induced paw oedema model, in which rats were pretreated orally with these compounds. In the hot-plate assay, BM113A and BM138A dose dependently prolonged the latency of the nociceptive reaction. Their analgesic activity, measured as a median effective dose (ED(50)=4.7 mg/kg), was similar to that of morphine (2.4 mg/kg). In the writhing test, all four compounds, in particular BM113A and BM138A, showed higher potency than the reference drug acetylsalicylic acid (the ED(50) values were 3.7, 2.3 and 46.1 mg/kg, respectively). BM138 caused a dose-dependent diminution of paw oedema (up to 49%) in the carrageenan model and BM138A at 200 mg/kg reduced mechanical hyperalgesia in the Randall-Selitto test (～30% when compared with the control). None of the γ-butyrolactone derivatives tested at the ED(50) obtained in the hot-plate test influenced the locomotor activity of mice, although in the rotarod test at 24 rpm, BM113A and BM138 at 100 mg/kg showed some motor-impairing properties. In vitro, a concentration-dependent ABTS radical cation-scavenging activity of BM138 and BM138A (up to 80% inhibition of the radical absorbance) was observed. The results of the present study suggest that BM138 and BM138A could be of interest for future investigations as antinociceptive and antioedematous agents with potential free radical-scavenging properties.     

Modulation of inflammatory paw oedema by cysteamine in the rat.

Cysteamine, a potent somatostatin depletor, was used in the present study to investigate the role of endogenous somatostatin in acute peripheral inflammation. The acute inflammation was induced by intraplantar injection of carrageenan (1%), histamine (5 micromol), or formalin (2.5%) in the rat hind paw. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Given subcutaneously (s.c.) 1 h before carrageenan, cysteamine caused significant, dose-dependent and long-lasting inhibition of rat paw oedema induced by carrageenan. At doses of 12.5, 25, 50 or 100 mg kg (-1), cysteamine significantly inhibited the carrageenan-induced paw oedema at 4 h by 52.3, 40, 40.7 or 26.3%. Cysteamine given at 300 mg kg (-1), a dose well known to deplete tissue somatostatin, reduced oedema by only 16.2% vs control values. Significant inhibition of the carrageenan-induced rat paw oedema was still evident 24 h post-injection at cysteamine doses of 12.5, 25, 50 or 100 mg kg (-1). Given s.c. at 300 mg kg (-1), 4 h prior to carrageenan, cysteamine decreased rat paw oedema at 4 h by 14.9%. Cysteamine (300 mg kg (-1)), 4 h beforehand, had little modulatory effect on the oedema induced by formalin (2.5%) but reduced that caused by intraplantar histamine (5 micromol). The anti-oedematogenic effect of indomethacin, but not that of the selective COX-2 inhibitor celecoxib, was less marked in rats pre-treated with cysteamine at 300 mg kg (-1). Cysteamine (0.3 microg- 0.3 mg paw (-1)) co-administered with carrageenan was devoid of anti-inflammatory effect and even promoted inflammation at low concentrations. Cysteamine given locally alone induced slight paw oedema. These data indicate that systemic cysteamine possesses potent and long-lasting anti-inflammatory effects and modulates the anti-inflammatory effect of cyclooxygenase inhibitors in a model of peripheral inflammation in the rat. The effect of cysteamine is likely to be mediated via central action.     

Studies on the anti-inflammatory effect of fluoxetine in the rat.

The anti-inflammatory activity of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), was studied on the carrageenan-induced paw inflammation in the rat. Fluoxetine (10-60 mg kg(-1)) given intraperitoneally (i.p.) 30 min before carrageenan, displayed marked anti-inflammatory activity, inhibiting paw oedema by 38.6-77.7% at 2 h post-carrageenan. Fluoxetine administered at time of carrageenan injection or 30 min after carrageenan challenge, markedly inhibited the paw oedema response. Rats administered daily fluoxetine (20 mg kg(-1), i.p.) showed significantly decreased inflammatory response to subplantar carrageenan when examined on the 5th and 14th day of fluoxetine injection. Fluoxetine (10 or 20 mg kg(-1), i.p.) co-administered with indomethacin (IND) (20 mg kg(-1), i.p.), celecoxib (10 mg kg(-1), i.p.) or rofecoxib (4.5 mg kg(-1), i.p.) before carrageenan reduced the anti-oedema effect of indomethacin or celecoxib, but had additive effect to that of rofecoxib. The anti-oedema effects of fluoxetine and melatonin or the tricyclic antidepressant imipramine were additive. In contrast, administration of both fluoxetine and the heterocyclic antidepressant trazodone had no greater anti-inflammatory effect than fluoxetine alone. The anti-oedema effect of fluoxetine was partially suppressed by the opioid antagonist naloxone (4 mg kg(-1), i.p.). Fluoxetine (360 or 720 microg per paw) given into the rat paw with carrageenan reduced the oedema response by 25.4 and 35.3% 4 h post-carrageenan, respectively. It is suggested that fluoxetine alone or co-administered with either imipramine or melatonin would be of benefit in the sitting of neuropathic or inflammatory pain conditions. Both the serotonergic and the opioid systems are likely to be involved in the modulating action of fluoxetine on peripheral inflammation.     

Anti-inflammatory and analgesic activities of the aqueous extract of Acacia karroo stem bark in experimental animals

The aqueous extract of the stem bark of Acacia karroo Hayne was investigated for its anti-inflammatory and analgesic activities in animal models. The extract at 100 and 200 mg/kg reduced significantly the formation of oedema induced by carrageenan and histamine. In the acetic acid-induced writhing model, the extract showed a good analgesic effect characterized by a significant reduction in the number of writhes with two doses (100 and 200 mg/kg) used when compared to the untreated control group. In the tail immersion test, the extract at the doses used (100 and 200 mg/kg) increased reaction time to pain after 30 min. of oral administration of the extract. Indomethacin at 10 mg/kg served as reference drug in all these tests. The results gave a scientific basis to the traditional uses of Acacia karroo mainly for wound poultices, eye treatments and cold remedies.