Evaluation of anti-pyretic potential of Jussiaea suffruticosa L. extract in rats.

A study was carried out to evaluate the anti-pyretic potential of the methanol extract of the aerial part of Jussiaea suffruticosa Linn. (MEJS) on normal body temperature and yeast-induced pyrexia in albino rats. Yeast suspension (10 ml/kg body wt.) increased rectal temperature after 19 hours of subcutaneous injection. The MEJS, at doses of 100, 200 and 300 mg/kg body wt. p.o., showed significant reduction in normal body temperature and yeast-provoked elevated temperature in a dose-dependent manner. The effect also extended up to 5 hours after the drug administration. The anti-pyretic effect of MEJS was comparable to that of paracetamol (150 mg/kg body wt, p.o.), a standard anti-pyretic agent.     

Evaluation of anti-pyretic potential of Ficus racemosa bark.

A study was carried out to evaluate the anti-pyretic effect of a methanol extract of stem bark of Ficus racemosa Linn. (MEFR) on normal body temperature and yeast-induced pyrexia in albino rats. A yeast suspension (10 ml/kg body wt.) increased rectal temperature 19 h after subcutaneous injection. The MEFR, at doses of 100, 200 and 300 mg/kg body wt. p.o., showed significant dose-dependent reduction in normal body temperature and yeast-provoked elevated temperature. The effect extended up to 5 h after drug administration. The anti-pyretic effect of MEFR was comparable to that of paracetamol (150 mg/kg body wt., p.o.), a standard anti-pyretic agent.     

Evaluation of antipyretic activity of leaf extracts of Mallotus peltatus (Geist) Muell. arg. var acuminatus: a folk medicine.

A study was carried out to evaluate the anti-pyretic potential of the methanol extract of Mallotus peltatus (Geist) Muell. Arg. var acuminatus leaf, a folk medicine of Onge tribes of Bay Islands, on normal body temperature and yeast-induced pyrexia in Wister albino rats. The leaf extract at oral doses of 100, 200 and 300 mg kg(-1), p.o., showed significant reduction in normal body temperature and yeast-provoked elevated temperature in a dose-dependent manner and the anti-pyretic effect was comparable to that of standard anti-pyretic agent paracetamol (150 mg kg(-1), p.o.). The effect also extended up to 5 hours after the drug administration.     

Analgesic and antiinflammatory effects of chalcones isolated from Myracrodruon urundeuva allem?o.

The present work showed analgesic and antiinflammatory activities from a fraction containing three dimeric chalcones (chalcone enriched fraction - CEF), isolated from the stem-bark ethyl acetate extract of Myracrodruon urundeuva Allemao (Anacardiaceae). M. urundeuva is a popular medicinal plant used widely in Northeast Brazil, mainly as a topical female genital tract antiinflammatory. We observed that the CEF (5 and 10 mg/kg body wt., i.p. or p.o.) inhibited acetic acid-induced abdominal contractions in mice. In the formalin test, the CEF (5 and 10 mg/kg body wt.) was more effective intraperitoneally and inhibited predominantly the second phase of response. Naloxone reversed this effect, indicating an involvement of the opioid system. The CEF (10 and 20 mg/kg body wt.) also increased the reaction time to thermal stimuli in the hot-plate test in mice, after i.p. but not after p.o. administration. In the carrageenan-induced paw edema test in mice, the CEF (20 and 40 mg/kg body wt.) decreased paw volume significantly, after i.p. administration 2-4 hours after carrageenan injection. The CEF (40 mg/kg body wt.) was also active orally during the same period of time. The present work is the first report on peripheral and central analgesic effects and antiinflammatory activity of natural dimeric chalcones.     

Solanum paniculatum L. (Jurubeba): potent inhibitor of gastric acid secretion in mice.

Solanum paniculatum L. is used commonly in Brazilian folk medicine for the treatment of liver and gastrointestinal disorders. The freeze-dried aqueous extracts (WEs) obtained from distinct parts of the plant (flowers, fruits, leaves, stems and roots) were tested to determine their antiulcer and antisecretory gastric acid activities using mice. The aqueous extracts of roots, stems and flowers inhibited gastric acid secretion in pylorus-ligated mice with ED50 values of 418, 777 and 820 mg/kg body wt. (i.d.), respectively. Extracts of leaves (0.5-2 g/kg body wt., i.d.) did not affect gastric secretion, whereas fruit extracts (0.5-2 g/kg body wt., i.d.) stimulated gastric acid secretion. The stimulatory effect of the fruit extract was inhibited by pretreatment with atropine (5 mg/kg body wt., i.m.) but not with ranitidine (80 mg/kg body wt., i.p.) suggesting that the fruit extract activates the muscarinic pathway of gastric acid secretion. In contrast, administration of the root extract into the duodenal lumen inhibited histamine- and bethanechol-induced gastric secretion in pylorus-ligated mice. In addition, the aqueous extract of roots (ED50 value, 1.2 g/kg body wt., p.o.) protected the animals against production of gastric lesions subsequent to the hypersecretion induced in mice by stress following cold restraint. This effect was not reproduced when the lesions were induced by blockade of prostaglandins synthesis via subcutaneous injection of indomethacin. Thus, antiulcer activity of the plant extracts appears to be related directly to a potent anti-secretory activity. No toxic signs were observed following administration of different extracts up to 2 g/kg body wt., p.o. Collectively, the results validate folk use of Solanum paniculatum L. plant to treat gastric disorders.     

Investigations of the methanolic leaf extract of Costus afer. Ker for pharmacological activities in vitro and in vivo.

The methanolic leaf extract of Costus afer. Ker (family: Zingiberaceae) was investigated for some pharmacological effects in vivo and in vitro. Brine shrimp lethality test showed that the extract was significantly (p < 0.05) cytotoxic with LC50 of 21.3 ppm. The extract showed moderate local anesthetic property, about twice less than lignocaine of the same concentration, on guinea pig wheal test. The extract contracted the guinea pig ileum in a concentration-dependent manner, but had no effect on pleuripara and nullipara non-gravid uteri at progestogenic and estrogenic phases respectively. The contractile effect on the guinea pig ileum was partially inhibited by atropine but completely reversed by adrenaline. The extract induced expulsion of whole fetuses still enveloped within the placental membrane at the 3rd trimester of pregnancy. The extract exhibited a biphasic antihyperglycemic activity. At 200 mg/kg body wt., p.o., it decreased the blood glucose level by 50% in Streptozotocin-induced hyperglycemia in male rats in 60 minutes post dosing. However, doses above 200 mg/kg body wt., p.o., caused increase in blood glucose level, potentiating the action of STZ. At 10 microg/ml the extract induced about 98% glucose uptake in differentiated 3T3-L1 adipocytes when compared with insulin (340 nm).     

Agastache mexicana may produce anxiogenic-like actions in the male rat.

Behavioral effects of a water-soluble extract of Agastache mexicana, a plant with purported anxiolytic actions, were studied in male Wistar rats. In the elevated plus-maze test, various doses of the plant extract (3.0 mg/kg body wt.; 9.0 mg/kg body wt.; 12.0 mg/kg body wt.) administered intraperitoneally (i.p.) decreased the exploration of open arms, showing an anxiogenic-like effect. Agastache mexicana (12 mg/kg body wt.; i.p.) did not change immobility in the forced swimming test (i.e., had no anti-depressant effect) but increased the anti-immobility action of 32.0 mg/kg body wt. (i.p.) of desipramine (i.e., increased the antidepressant-like effect of desipramine). A. mexicana had no effect on exploratory activity in an open field test, indicating that it had no sedative effect at the doses used. It is concluded that effects of the water extract of A. mexicana are more consistent with an anxiogenic-like property than an anxiolytic-like one.     

Antiinflammatory and chronic toxicity study of the leaves of Ageratum conyzoides L. in rats

The hydroalcoholic extract (HAE) of Ageratum conyzoides leaves was studied for its antiinflammatory effect on subacute (cotton pellet-induced granuloma) and chronic (formaldehyde-induced arthritis) models of inflammation in rats. The absence or presence of toxicity by prolonged use of HAE was also evaluated through biochemical and hematological analysis of rats blood samples using daily oral doses of 250 or 500 mg/kg body wt., during 90 days. The results showed that the group of rats treated with HAE (250 mg/kg body wt.; p.o.) had a 38.7% (p < 0.05) reduction in cotton-pellet granuloma. The development of chronically induced paw edema was also reduced significantly (p < 0.05) by the plant extract. The toxicity study did not show any treatment-related abnormalities in biochemical and hematological parameters. The biochemical analysis from blood samples drawn from group of rats treated orally with 500 mg/kg body wt. did, however, present 30.2% (p < 0.05) reduction of SGPT activity as compared to the corresponding control group. These results confirm the antiinflammatory properties of A. conyzoides, with no apparent hepatotoxicity.     

Evaluation of anti-tussive activity of Bergenia ciliata Sternb. rhizome extract in mice.

The methanol extract of the rhizome of Bergenia ciliata Sternb. (Saxifragaceae) has been evaluated for its potential in a cough model induced by sulphur dioxide gas in mice. The extract exhibited significant anti-tussive activity in a dose-dependent manner, as compared with control. The antitussive activity of the extract was comparable to that of codeine phosphate (10 mg/kg body wt.), a standard anti-tussive agent. The extract at doses of 100, 200 and 300 mg/kg body wt. (p.o.) showed significant inhibition of cough reflex by 28.7, 33.9 and 44.2%, respectively, within 90 min of the experiment.     

Effect of Ruta graveolens L. and Euphorbia peplus L. anti-inflammatory extracts on nutritional status of rats and the safety of their use

A significant increase in body weight with remarkable increase in total food intake and significant increase in protein efficiency ratio were observed following oral administration of R. graveolens ether extract (500 mg/kg body wt) to growing rats for 3 weeks. Serum albumin was significantly decreased after administration of declofenac (15 mg/kg body wt). Albumin/globulin ratio decreased significantly on administration of E. peplus ether extract (500 mg/kg body wt). No significant changes were observed in other biochemical and nutritional parameters on administration of either of the extracts or declofenac. However, only a significant elevation of alkaline phosphatase was noticed during treatment with R. graveolens. The results suggest that both plant extracts have no harmful effect on nutritional status and are safe towards kidney functions, while Euphorbia is more safe than Ruta in relation to liver functions.     

Anti-diabetic potential of Barleria lupulina extract in rats.

We have undertaken a study to evaluate the anti-hyperglycemic effect of a methanol extract of aerial parts of Barleria lupulina Lindl. (Acanthaceae) in streptozotocin-diabetic rats, based on folkloric reports its use as an anti-diabetic agent. The extract exerted significant (p < 0.05) anti-hyperglycemic efficacy at all levels tested from 4 h after its administration, as compared with the control group, and the effect was also prolonged up to 12 h. The extract at doses of 200 mg kg(-1) body wt. and above exhibited a maximum activity (p < 0.001) at 12 h after administration. The most significant activity (15.35% blood glucose reduction) was observed for the group administered 300 mg kg(-1) body wt. at 12 h after administration, while the standard drug glibenclamide (10 mg/kg(-1) body wt.) showed an 18.80% reduction of blood glucose at the same time interval. Based on our current results, it appears that the methanol extract of aerial parts of Barleria lupulina Lindl. shows a pronounced blood-glucose-lowering potential in streptozotocin hyperglycemic rats, and is thus provided with a pharmacological support of the folklore claims of anti-diabetic activity.     

Antiulcer activity of Andrographis paniculata (Burm.f.) wall. against cysteamine-induced duodenal ulcer in rats

Antiulcer activity of Andrographis paniculata was evaluated by cysteamine induced duodenal ulcer model in rats. Male albino Wistar rats were pre-administered with 200 mg/kg body wt. of hydroalcoholic extact of Andrographis paniculata (HAEAP) orally, for 30 days prior to i.p. administration of 420 mg/kg body wt. of cysteamine as a single dose. Rats preadministered with 30 mg/kg body wt. of ranitidine served as standard drug. Ulcer index, thiobarbituric acid reactive substances, mucin, glutathione peroxidase and myeloperoxidase activities, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, glycoproteins and membrane bound enzyme activities were measured in duodenum of experimental animals. The ulcer score and myeloperoxidase activity were significantly minimized in rats treated with HAEAP. Mucin content was found to be preserved in rats treated with the extract. GSH/GSSG ratio and glutathione peroxidase activities were found to be maintained by the HAEAP. Level of lipid peroxidation products was found to be significantly low in HAEAP treated rats compared to ulcer control rats. The basolateral and brush border membrane bound enzyme activities which were depleted significantly in ulcer control rats were found to be maintained in rats pre-treated with the extract. The ulcer preventing effect was comparable to that of ranitidine treated rats. Level of glycoproteins was also found to be preserved in rats treated with the extract. The normal rats treated with the HAEAP did not show any abnormal alterations in the parameters studied. Histopathological observations also showed the ulcer preventing effect of the HAEAP. It is suggested that the ulcer preventing effect may be due to its mucin preserving and antioxidant nature.     

Analgesic and anti-inflammatory activities of a fraction rich in oncocalyxone A isolated from Auxemma oncocalyx.

In the present work we studied the antinociceptive and antiedematogenic effects of a quinone fraction (QF) isolated from the heartwood of Auxemma oncocalyx Taub. The major constituent of QF, which represented around 80% of this fraction, was a terpenoid quinone named oncocalyxone A (1). Results show that QF (10 and 30 mg/kg body wt., i.p.) significantly inhibited paw edema induced by carrageenan at the second, third, and fourth hours. The effect was dose-dependent and long lasting, and QF was less effective orally. An antiedematogenic effect was also demonstrated in the dextran-induced paw edema. In this model, however, QF was somewhat less potent. QF (1 and 5 mg/kg body wt., i.p.) inhibited acetic acid-induced abdominal contractions in mice in a dose-dependent manner. In addition, QF (5 and 10 mg/kg body wt., i.p.) inhibited only the second phase (inflammatory) in the formalin test, and showed no effect in the hot-plate test in mice. The antinociceptive activity of QF was predominantly peripheral and independent of the opioid system. The observed effects of QF are, at least in part, probably due to the presence of oncocalyxone A (1).     

Hepatoprotective effect of aqueous extract of Phyllanthus niruri on nimesulide-induced oxidative stress in vivo

Nimesulide (NIM), an atypical non-steroidal anti-inflammatory drug (NSAID) is also used as analgesic. In the present study, we evaluated its effect on the prooxidant-antioxidant system of liver and the hepatoprotective potential of aqueous extract of the herb Phyllanthus niruri (PN) on NIM-induced oxidative stress in vivo using a murine model, by determining the activities of hepatic anti-oxidant enzymes superoxide dismutase (SOD) and catalase (CAT), levels of reduced glutathione (GSH) and lipid peroxidation (expressed as malonaldialdehyde, MDA). Aqueous extract of PN at a dose of 50 or 100 mg/kg body wt was administered either intraperitoneally or orally for 7 days, before NIM administration at a dose of 8 mg/kg body wt twice daily for 7 days in mice. Animals were sacrificed 24 h after administration of final dose of NIM. In another set of experiments, both aqueous extract of PN (at a dose of 50 or 100 mg/kg body wt) and NIM (8 mg/kg body wt) were administered simultaneously for 7 days. Animals were sacrificed 24 h after administration of final dose of the extract and NIM, liver tissues were collected, and the activities of SOD and CAT and levels of GSH and lipid peroxidation end-product (as MDA), were determined from the livers of all the experimental animals. Appropriate NIM control was maintained for all sets of experiments. NIM administration (8 mg/kg body wt) for 7 days caused significant depletion of the levels of SOD, CAT and reduced GSH, along with the increased levels of lipid peroxidation. Intraperitoneal administration of the extract at a dose of 50 mg/kg body wt for 7 days,. prior to NIM treatment, significantly restored most of the NIM-induced changes and the effect was comparable to that obtained by administering 100 mg/kg body wt of the extract orally. Thus, results suggested that intraperitoneal administration of the extract could protect liver from NIM-induced hepatic damage more effectively than oral administration. Antioxidant property of the aqueous extract of PN was also compared with that of a known potent antioxidant, vitamin E. The PN extract at a dose of 100 mg/kg body wt along with NIM was more effective in suppressing the oxidative damage than the PN extract at a dose of 50 mg/kg body wt. Results suggested that beneficial effect of the aqueous extract of PN, probably through its antioxidant property, might control the NIM-induced oxidative stress in the liver.     

Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory activity, analgesic effect and fetus toxicity of a crude leaf extract

Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows widely along the southeastern coast of Brazil. Its leaves have been used in folk medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We have already described the anti-inflammatory properties of C. verbenacea and its low toxicity in different acute animal models. In the present study, we investigated the anti-inflammatory activity in sub-chronic animal models of a crude leaf lyophilized extract when administered by oral route or topically applied, and concomitantly, its analgesic potency and toxicity to the fetus. Topical administration of the extract inhibited nystatin-induced edema proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt., orally administered, has a very similar effect as compared to nimezulide (2.5 mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48 mg/kg body wt. the extract showed a very low analgesic effect, and total absence of fetus toxicity at doses of less than 7.44 mg/kg body wt.     

Evaluation of the analgesic activity of extracts of Miconia rubiginosa (Melastomataceae)

The analgesic effects of the hexane, methylene chloride and ethanol extracts of Miconia rubiginosa were evaluated in mice and rats using the acetic acid-induced writhing and hot plate tests. The extracts (100, 200 and 300 mg/kg body wt.) and indomethacin (5 mg/kg body wt.) produced a significant (p < 0.05 and p < 0.01) inhibition of acetic acid-induced abdominal writhing. These same extracts (200 mg/kg body wt.) showed a significant (p < 0.05) antinociceptive effect, lower than that produced by morphine (4 mg/kg body wt.). The fractionation of the methylene chloride extract yielded ursolic and oleanoic acids as the major compounds. Using only gas chromatography, it was possible to identify the following triterpenes in the hexane extract: alpha-amyrin, beta-amyrin, lupeol and beta-sitosterol.     

Antinociceptive effects of the essential oil of Alpinia zerumbet on mice.

Alpinia zerumbet (Pers.) Burtt. et Smith is an aromatic plant that is distributed widely in the tropical and sub-tropical regions of the world. In Brazil, where A. zerumbet is called "colonia", it is used widely in folk medicine for the treatment of various diseases, including hypertension. In the present study, the antinociceptive effects of the orally administered essential oil of A. zerumbet (EOAz) were evaluated in male Swiss mice (20-25 g each). In the acetic acid-induced writhing test, EOAz (30, 100 and 300 mg/kg body wt.; n = 10, n = 13 and n = 15, respectively) was effective at all doses. In the hot-plate test, EOAz significantly increased the latency at doses of 100 and 300 mg/kg body wt., but not at 30 mg/kg body wt., at all observation times up to the 180th min (n = 10 for each dose). In the formalin test, EOAz significantly reduced paw licking time in the second phase of the test at 100 mg/kg body wt. (n = 10), but decreased it in both phases at 300 mg/kg body wt. (n = 10). At 30 mg/kg body wt., the effect of EOAz did not differ from control values in either phase of the formalin test (n = 10). Pretreatment with naloxone (5 mg/kgbodywt., i.p.) caused a significant reversal of the analgesic effect of 300 mg/kg body wt. EOAz (n = 8) that was complete for the first phase, but only partial for the second phase of the formalin test. The data show that orally administered OEAz promotes a dose-dependent antinociceptive effect, with a mechanism of action which probably involves the participation of opiate receptors.     

Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown.

Citral, myrcene and limonene (100 and 200 mg/kg body wt., i.p.), constituents of essential oils from Lippia alba chemotypes, decreased not only the number of crossings but also numbers for rearing and grooming, as measured by the open-field test in mice. Although muscle relaxation detected by the rota rod test was seen only at the highest doses of citral (200 mg/kg body wt.) and myrcene (100 and 200 mg/kg body wt.), this effect was observed even at the lowest dose of limonene (50 mg/kg body wt.). Also, citral and myrcene (100 and 200 mg/kg body wt.) increased barbiturate sleeping time as compared to control. Limonene was also effective at the highest dose, and although citral did not increase the onset of sleep, it increased the duration of sleep, which is indicative of a potentiation of sleeping time. Citral (100 and 200 mg/kg body wt.) increased 2.3 and 3.5 times, respectively, the barbiturate sleeping time in mice. Similar effects were observed for myrcene and limonene at the highest dose (200 mg/kg body wt.) which increased the sleeping time around 2.6 times. In the elevated-plus maze, no effect was detected with citral up to 25 mg/kg body wt., while at a high dose it decreased by 46% the number of entries in the open arms. A smaller but significant effect was detected with limonene (5 mg/kg body wt.). While myrcene (10 mg/kg body wt.) decreased only by 22% the number of entries in the open arms, this parameter was decreased by 48% at the highest dose. Our study showed that citral, limonene and myrcene presented sedative as well as motor relaxant effects. Although only at the highest dose, they also produced a potentiation of the pentobarbital-induced sleeping time in mice, which was more intense in the presence of citral. In addition, neither of them showed an anxiolytic effect, but rather a slight anxiogenic type of effect at the higher doses.     

Hypoglycemic effect of Sclerocarya birrea {(A. Rich.) Hochst.} [Anacardiaceae] stem-bark aqueous extract in rats

This study was undertaken to evaluate the hypoglycemic effect of Sclerocarya birrea [(A. Rich.) Hochst.] subspecies caffra (Sond.) Kokwaro [family: Anacardiaceae] stem-bark aqueous extract in normal (normoglycemic) and in streptozotocin (STZ)-treated, diabetic Wistar rats. In one set of experiments, graded doses of S. birrea stem-bark aqueous extract (SB, 100-800 mg/kg p.o.) were separately administered to groups of fasted normal and fasted diabetic rats. In another set of experiments, a single dose of the plant aqueous extract (SB, 800 mg/kg p.o.) was used. The hypoglycemic effect of this single dose (SB, 800 mg/kg p.o.) of S. birrea stem-bark aqueous extract was compared with that of chlorpropamide (250 mg/kg p.o.) in both fasted normal and fasted diabetic rats. Following acute treatment, relatively moderate to high doses of S. birrea stem-bark extract (SB, 100-800 mg/kg p.o.) produced dose-dependent, significant reductions (P < 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. Chlorpropamide (250 mg/kg p.o.) also produced significant reductions (P < 0.05-0.001) in the blood glucose concentrations of the fasted normal and fasted diabetic rats. Administrations of the single dose of S. birrea stem-bark aqueous extract (SB, 800 mg/kg p.o.) significantly reduced (P 0.01 < 0.001) the blood glucose levels of both fasted normal (normoglycemic) and fasted STZ-treated, diabetic rats. The results of this experimental animal study indicate that aqueous extract of Sclerocarya birrea possesses hypoglycemic activity, and thus lend credence to the suggested folkloric use of the plant in the management and/or control of adult-onset, type-2 diabetes mellitus in some African communities.     

Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems

The aim of the present study was to evaluate the effects of safranal, an active constituent of Crocus sativus L. stigmas, on seizures induced by pentylenetetrazol. Intracerebroventricular (i.c.v.) microinjection of safranal (4.84, 9.68 and 24.2 micromol) had no effects on tonic and clonic phases as well as mortality upon seizures induced by PTZ (90mg/kg body wt., i.p.). Peripheral administration of safranal (72.75, 145.5 and 291 mg/kg body wt., i.p.), however, induced a dose-dependent decrease in the incidence of both minimal clonic seizures (MCS) (145.5 mg/kg body wt., p<0.01) and generalized tonic-clonic seizures (GTCS) (145.5 mg/kg body wt., p<0.001) following PTZ administration. Safranal also increased MCS and GTCS latency, significantly. Percent of protection against GTCS was 30%, 100% and 100% and mortality protection percent was 40%, 100% and 100% for the mentioned doses, respectively. Pretreatment with flumazenil (5 nmol, i.c.v.) and naloxone (5.5 nmol, i.c.v. and 2 mg/kg body wt., i.p.), 15 min prior to safranal administration (145.5 mg/kg body wt., i.p.), abolished the protective effect of safranal on MCS. Flumazenil also decreased the effect of safranal on incidence as well as latency of GTCS, significantly. These effects were not, however, significant for naloxone (5.5 nmol, i.c.v. and 2mg/kg body wt., i.p.). Results of this study demonstrated that safranal could exert anticonvulsant activity in the PTZ model and this effect may be mediated, at least partly, through GABA(A)-benzodiazepine receptor complex.