Lycopene attenuates silver nanoparticle-induced liver injury in albino mice.

Lycopene is a carotenoid widely used for its dominant antioxidant properties and beneficial health effects. Silver nanoparticles (AgNP) have gained attention for use in many medicinal and consumer products, leading to animal, human, and environmental exposure. This study investigated the dose-dependent effects of lycopene on AgNP-induced hepatotoxicity in albino mice. The four experimental groups, comprising eight albino mice each, were as follows: Group I, vehicle control (C); Group II, AgNP-treated (5 mg/kg/day) (AgNP); Group III, AgNP/lycopene-treated (5 + 10 mg/kg/day) (AgNP + LP10); and Group IV, AgNP/lycopene-treated (5 + 100 mg/kg/day) (AgNP + LP100). All solutions were orally administered to the mice once in a day for consecutive 14 days. The levels of serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and total bilirubin were significantly higher in the AgNP-treated group than in the control group but significantly lower in the AgNP + LP100 group than in the AgNP-treated group. A significant decrease in reduced glutathione level and superoxide dismutase activity and an increase in lipid peroxidation were observed in the AgNP-treated group; these were significantly suppressed in the AgNP+LP100 as compared to AgNP-treated group. Histopathological examination showed substantial morphological alterations in hepatic tissues in the AgNP, which were adequately improved in the low and high dose lycopene-treated groups. The dose of 100 mg/kg/day of lycopene was more effective than 10 mg/kg/day, as pretreatment with high dose lycopene significantly diminished the adverse changes occurred due to AgNP in liver weight, hepatic architecture, serum functional markers, and antioxidant markers. Thus, present study shows that pretreatment with lycopene offers protection against AgNP-induced hepatotoxicity and oxidative stress.

In vitro and in vivo evaluation of probiotic potential and safety assessment of Bacillus coagulans SKB LAB-19 (MCC 0554) in humans and animal healthcare.

Bacillus coagulans is Gram positive, spore forming and high lactic acid producing bacteria; however, probiotic and safety assessment of the isolated strain need to be investigated for commercial applications. Current study aimed to screen SKB LAB-19 for potential probiotic characteristics viz. enzyme production, antimicrobial properties, pH/bile salt tolerance, temperature stability, antidiarrheal activity in Swiss albino mice and Wistar rats; and acute oral toxicity in mice. The results showed that, SKB LAB-19 produces eight potential enzymes, effective against E. coli and C. perfringensis, tolerant to bile salt (0.3%w/v)/gastric pH (2.5), stable at 40-90 °C and nontoxic to cells. SKB LAB-19 was found to be safe and displayed promising results to reverse E. coli and castor oil induced diarrhoea. Histopathological studies showed repair to damaged mucosal epithelium cells and improves integrity of the goblet cells of colon. SKB LAB-19 showed immunomodulatory effects with increased immunoglobulins in blood and augmented weight of spleen and thymus. In addition, SKB LAB-19 showed significant in-vitro antioxidant activity (82.93%), reducing capacity and ascorbate auto-oxidation inhibition effect (94.62%). These preliminary results suggested that, SKB LAB-19 was found to be safe and has the potential to be used as effective probiotic and anti-diarrhoeal agent in humans and animal healthcare.

Protective effect of SKB_Gutbiotic against castor oil and E.coli induced diarrhea in laboratory animals.

The aim of this study is to evaluate antidiarrheal activity of SKB_Gutbiotic against Castor oil and E.coli induced diarrhea in Swiss albino mice and Sprague Dawley rats. In present study three doses of SKB_Gutbiotic were tested against castor oil induced diarrhea in mice. Its effect on co-administration with l-arginine was studied. SKB_Gutbiotic delayed onset of diarrhea, reduced fecal output and fecal weight. In Gastrointestinal transit time and Castor oil induced enteropooling, SKB_Gutbiotic significantly reduced peristaltic index and volume of intestinal content respectively. In E.coli induced diarrhea model, E.coli suspension was administered for 3 days for inducing diarrhea. SKB_Gutbiotic significantly and dose dependently reduced fecal output, improved fecal consistency, reduced fecal water content and improved WBC count. Histopathological images showed improvement in damage caused to the mucosal epithelium due to E.coli and also improved complete crypt cell architecture and integrity of goblet cells. These results indicated that SKB_Gutbiotic can be used as an antidiarrheal agent against castor oil and E.coli induced diarrhea. It inhibits colonization of E.coli bacteria on colonic epithelium which results into decreased intestinal hypersecretion and motility which is very useful in the management of infectious diarrhea. Thus SKB_Gutbiotic could be an effective alternative to standard antidiarrheal drugs.

Effect of ethanolic extract of Coriandrum sativum L. on tacrine induced orofacial dyskinesia.

The effect of ethanolic extract of Coriandrum sativum L. seeds (100, 200 mg/kg) was studied on tacrine induced orofacial dyskinesia. Tacrine (2.5 mg/kg, i.p.) treated animals were observed for vacuous chewing movements (VCM), tongue protrusions (TP) and orofacial bursts (OB) for 1 h followed by observations for locomotor changes and cognitive dysfunction. Sub-chronic administration of Coriandrum sativum L. seed extract (E-CS) (100, 200 mg/kg, p.o., for 15 days significantly (P < 0.05) decreased the tacrine induced VCM, TP and OB; and also significantly (P < 0.05), increased locomotion and cognition compared to the tacrine treated group. Biochemical analysis revealed that tacrine administration significantly (P < 0.05) decreased the levels of superoxide dismutase (SOD), Catalase (CAT), glutathione reductase (GSH) levels and also significantly (P < 0.05) increased lipid peroxidation (LPO) as an index of oxidative stress, whereas subchronic administration of E-CS significantly (P < 0.05) improved the antioxidant enzyme (i.e. SOD, CAT, and GSH) levels and also significantly (P < 0.05) decreased lipid peroxidation (LPO). The results have demonstrated the protective role of ethanolic extract of Coriandrum sativum. L against tacrine induced orofacial dyskinesia.

Intravenous human umbilical cord blood improves electrophysiological and metabolic properties in ISO induced myocardial necrosis in rats.

Rats treated with isoproterenol (ISO, 85 mg/kg, sc, twice at an interval of 24 h) showed a significant increase in heart rate, mean arterial blood pressure, pressure rate index, ST elevation on ECG, and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum and a significant reduction in superoxide dismutase, and catalase and increase in thiobarbituric acid reactive substance activity in heart tissue. Treatment with Human umbilical cord blood (hUCBC; 500 and 1000 microL, iv, via the tail vein; 2 h after the second dose of ISO) significantly restored back to normal levels and showed a lesser degree of cellular infiltration and infarct size in histopathological and planimetry studies respectively. Thus, hUCBC ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of myocardial infarction.

Effect of pomegranate juice on Angiotensin II-induced hypertension in diabetic Wistar rats.

Acute subcutaneous administration of Angiotensin II (Ang II) causes a rise in blood pressure in diabetic Wistar rats. Diabetes was induced using streptozotocin (70 mg/kg, i.v.). Chronic administration of pomegranate juice (PJ) extract (100 mg/kg and 300 mg/kg; p.o. for 4 weeks) obtained from Punica granatum (punicaceae) fruits reduced the mean arterial blood pressure and vascular reactivity changes to various catecholamines and also reversed the biochemical changes induced by diabetes and Ang II. PJ treatment also caused a significant decrease in levels of thiobarbituric acid reactive substances (TBARS) in kidney and pancreas while activities of enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) showed significant elevation. The cumulative concentration response curve (CCRC) of Ang II was shifted towards right in rats treated with PJ using isolated strip of ascending colon. In histopathological examination, PJ treatment prevented the tubular degenerative changes induced by diabetes. The results suggest that the PJ extract could prevent the development of high blood pressure induced by Ang II in diabetic rats probably by combating the oxidative stress induced by diabetes and Ang II and by inhibiting ACE activity. In conclusion, PJ has antihypertensive action in Ang II diabetic model.

Effect of myricetin on blood pressure and metabolic alterations in fructose hypertensive rats.

Fructose feeding induces a rise in blood pressure in normal rats and is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. We have examined the effect of myricetin (100 and 300 mg/kg, p.o. for 6 weeks) isolated from Vitis vinifera Linn. (Vitaceae) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, and insulin in fructose-induced hypertension. Myricetin reduced systolic blood pressure and vascular reactivity changes to catecholamines and reversed the metabolic alterations induced by fructose. The cumulative concentration-response curve (CCRC) of Ang II was shifted toward the right in rats treated with myricetin, using isolated strips of ascending colon. The results suggest that myricetin could prevent the development of high blood pressure induced by a diet rich in fructose, probably by reversing the metabolic alterations induced by fructose. In conclusion, myricetin has antihypertensive action in the fructose model.

Cardioprotective potential of myricetin in isoproterenol-induced myocardial infarction in Wistar rats.

The study aimed to evaluate the protective role of myricetin obtained from Vitis vinifera (Vitaceae) on heart rate, electrocardiographic (ECG) patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphological and histopathological changes in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats. Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate and ST elevation in ECG, and a significant increase in the levels of cardiac marker enzymes - lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) in serum. Isoproterenol significantly reduced superoxide dismutase (SOD) and catalase (CAT) activity and increased vascular reactivity to various catecholamines. Pretreatment with myricetin (100 mg/kg, p.o. and 300 mg/kg, p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, levels of LDH, CK, AST, SOD, CAT, vascular reactivity changes and ECG patterns. Treatment with myricetin (100 mg/kg and 300 mg/kg) alone did not alter any of the parameters compared with vehicle treated Wistar rats. Myricetin treated animals showed a lesser degree of cellular infiltration in histopathological studies. Thus, myricetin (100 mg/kg and 300 mg/kg) ameliorates the cardiotoxic effects of isoproterenol and may be of value in the treatment of MI.

Antidepressant, anxiolytic and adaptogenic activity of torvanol A: an isoflavonoid from seeds of Solanum torvum.

The objective of this study was to determine the effect of torvanol A (10 and 30 mg/kg) isolated from Solanum torvum as antidepressant, anxiolytic and adaptogenic. Forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM) test, light dark apparatus (LDA), pentylenetetrazole-induced convulsions model and chronic stress-induced behavioural despair test were used. Torvanol A significantly (p < 0.05) decreased the immobility period, increased the time spent in open arms and entries in open arms, decreased the time spent in closed arms, increased the time spent in light area and decreased the time spent in dark area. Combination of torvanol A with various antagonists - prazocin(62.5 µg/kg, i.p.), para chloro phenyl alanine (pCPA) (100 mg/kg, i.p.) and haloperidol (50 µg/kg, i.p.) - has also produced the same effect in various behavioural parameters in FST, TST, EPM and LDA as the respective antagonists. This suggests involvement of noradrenergic, dopaminergic, serotonergic and gabaergic mechanisms.

Protective effect of Hypericum hircinum on doxorubicin-induced cardiotoxicity in rats.

Oxidative stress is the main factor in doxorubicin (DOX) induced cardiotoxicity. Wistar rats received either DOX (3 mg kg⁻¹, i.p.) every other day or combination of Hypericum hircinum (100 and 200 mg kg⁻¹, p.o.) and DOX or H. hircinum (200 mg kg⁻¹, p.o.) extract alone for 2 weeks. Cardiotoxicity was assessed by recording changes in ECG, heart rate and measuring the levels of cardiac marker enzymes--lactic acid dehydrogenase, creatine phosphokinase, glutamic oxaloacetic transaminase, the antioxidant defence enzymes--reduced glutathione (GSH), superoxide dismutase (SOD) and lipid peroxidative value (LPO) at the end of treatment schedule. Treatment with H. hircinum significantly (p < 0.05) decreased the levels of LPO and marker enzymes, increased the levels of GSH and SOD, reversed the changes in ECG and prevented the decrease in heart weight in DOX-treated group. The results suggest that H. hircinum has the potential to prevent the cardiotoxic effects induced by DOX.

Involvement of central noradrenaline, serotonin and dopamine system in the antidepressant activity of fruits of Solanum torvum (Solanaceae).

The methanolic extract (ME) of Solanum torvum seeds and its ethyl acetate fraction (EAF) were investigated for their antidepressant activity using behavioral (forced swim test, FST and tail suspension test, TST) and biochemical (monoamine oxidase, MAO reduced activity) tests. ME (10, 30 and 100 mg kg(-1)) and EAF (10 and 30 mg kg(-1)) dose dependently inhibited the immobility period, increased noradrenaline, serotonin and dopamine levels and inhibited the MAO enzymes in FST and TST using mice. Furthermore, we have observed antagonism between the threshold dose of ME (30 and 100 mg kg(-1)) and EAF (10 and 30 mg kg(-1)) with antagonists on behaviour mediated by neurotransmitters noradrenaline, serotonin and dopamine. MAO-A inhibition was more prominent as compared to MAO-B inhibition. The study provides evidence for antidepressant actions of S. torvum.

Effect of A-HRS on blood pressure and metabolic alterations in fructose-induced hypertensive rats.

Fructose feeding induces a rise in blood pressure in normal rats that is associated with insulin resistance, hyperinsulinemia, hyperglycaemia, hypercholesterolaemia and hypertriglyceridaemia. We have examined the effect of chronic administration of A-HRS (100 and 300 mg kg⁻¹; p.o.) isolated from Hibiscus rosa sinensis (Malvaceae) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, uric acid and insulin in fructose-induced hypertension model. A-HRS treatment (100 and 300 mg kg⁻¹, p.o. for 6 weeks) reduced SBP, vascular reactivity changes to catecholamines and reversed the metabolic alterations induced by fructose (10%) treatment for 6 weeks. The cumulative concentration response curve (CCRC) of angiotensin II (Ang II) was shifted towards the right in rats treated with A-HRS using an isolated strip of ascending colon. The results suggest that A-HRS could prevent the development of high-blood pressure induced by a diet rich in fructose, probably by reversing the metabolic alterations induced by fructose. In conclusion, A-HRS has an antihypertensive action in a fructose model.

Effect of myricetin on deoxycorticosterone acetate (DOCA)-salt-hypertensive rats.

Chronic administration of myricetin (100 and 300 mg kg⁻¹, p.o., for 4 weeks) isolated from Vitis vinifera (Vitaceae) ameliorated hypertension and oxidative stress induced by deoxycorticosterone acetate (DOCA)-salt in rats. Myricetin treatment reduced systolic blood pressure, vascular reactivity changes and reversed the DOCA-induced increase in heart rate. Urinary sodium excretion was significantly decreased in animals treated with myricetin compared to the DOCA group when measured by flame photometer. The cumulative concentration response curve of serotonin (5-HT) and angiotensin II (Ang II) were shifted towards the right in rats treated with myricetin using the isolated rat fundus strip and ascending colon, respectively. Increased levels of thiobarbituric acid reactive substances and decreased levels of superoxide dismutase, catalase and reduced glutathione in the heart tissue were observed in animals treated with DOCA, which were reversed by myricetin. Thus, myricetin shows antihypertensive and antioxidant properties in the DOCA model of hypertension.

Mucuna pruriens attenuates haloperidol-induced orofacial dyskinesia in rats.

Neuroleptic-induced tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic neuroleptic treatment. The agents improving dopaminergic transmission improve TD. Mucuna pruriens seed contains levodopa and amino acids. The effect of methanolic extract of M. pruriens seeds (MEMP) was studied on haloperidol-induced TD, alongside the changes in lipid peroxidation, reduced glutathione, superoxide dismutase (SOD) and catalase levels. The effect of MEMP was also evaluated in terms of the generation of hydroxyl and 1,1-diphenyl,2-picrylhydrazyl (DPPH) radical. MEMP (100 and 200 mg kg⁻¹) inhibited haloperidol-induced vacuous chewing movements, orofacial bursts and biochemical changes. MEMP also inhibited hydroxyl radical generation and DPPH. The results of the present study suggest that MEMP by virtue of its free radical scavenging activity prevents neuroleptic-induced TD.

Antidepressant activity of Ceratonia siliqua L. fruit extract, a source of polyphenols.

A previous study from our laboratory has shown the facilitatory effect of Ceratonia siliqua L. (Fabaceae) on the dopaminergic function. This study investigates the involvement of monoamines in the antidepressant activity of the total polyphenol content of Ceratonia siliqua extract (CS) in mice using a tail suspension test (TST) and forced swim test (FST). The immobility time in the TST and FST were significantly reduced by CS (25 and 50 mg kg(-1), i.p.). The extract considerably attenuated the duration of immobility induced by prazosin (62.5 µg kg(-1), i.p., an α-adrenoceptor antagonist) and eticlopride (0.1 µg kg(-1), i.p., a classical D2-like dopamine receptor antagonist) in both TST and FST, whereas the extract could not modify the immobility in mice treated with p-chlorophenylalanine (100 mg kg(-1), i.p., ×3 days; an inhibitor of serotonin synthesis) and baclofen (10 mg kg(-1), i.p., GABAB agonist). This suggests that the antidepressant effect of CS is mediated by dopamine and noradrenaline.

Korean ginseng extract attenuates reserpine-induced orofacial dyskinesia and improves cognitive dysfunction in rats.

Reserpine-induced orofacial dyskinesia in rats is an animal model of tardive dyskinesia that has been linked with free radical generation and oxidative stress. In the present study, reserpine (1 mg kg(-1), s.c.) was given to rats on days 1, 3 and 5 to induce orofacial dyskinesia, which is characterised by increased vacuous chewing and tongue protrusion. Sub-chronic treatment with Korean ginseng extract from day 1 to day 21 along with reserpine on days 1, 3 and 5 significantly and dose-dependently (100 and 200 mg kg(-1)) reduced reserpine-induced vacuous chewing movements and tongue protrusions. Reserpine-treated animals also showed poor retention of memory in the elevated plus maze paradigm. The sub-chronic Korean ginseng extract administration significantly reversed reserpine-induced retention deficits. Biochemical analysis revealed that repeated reserpine treatment significantly induced lipid peroxidation and decreased glutathione (GSH) levels in the brains of rats. Reserpine-treated rats also showed decreased levels of antioxidant defence enzymes, superoxide dismutase (SOD), and catalase. Sub-chronic administration of Korean ginseng extract dose-dependently and significantly reduced lipid peroxidation and restored decreased GSH levels by repeated reserpine treatment. It also significantly reversed the reserpine-induced decrease in brain SOD and catalase levels in rats. The present study concludes that oxidative stress might play an important role in reserpine-induced abnormal oral movements, and Korean ginseng extract could be useful in the treatment of drug-induced dyskinesia and amnesia.

Cardioprotective potential of Punica granatum extract in isoproterenol-induced myocardial infarction in Wistar rats.

OBJECTIVE: To determine the protective role of Punica granatum L. (Punicaceae) seed juice extract and its butanolic fraction on heart rate, electrocardiographic patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphologic and histopathological changes in isoproterenol-induced myocardial infarction in male Wistar rats. MATERIALS AND METHODS: The effects of Punica granatum seed juice extract (100 mg/kg, p.o. and 300 mg/kg, p.o.) and butanolic fraction of Punica granatum seed juice extract (100 mg/kg., p.o.) on cardiac parameters were studied. Isoproterenol hydrochloride was used to induce myocardial infarction in Wistar rats. At the end of the experiment, heart rate, ECG, pressure rate index and cardiac marker enzyme levels were assessed. RESULTS: Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate, ST elevation in ECG, pressure rate index and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum. Isoproterenol significantly reduced superoxide dismutase and catalase activity and increased vascular reactivity to various catecholamines. Pretreatment with PJ (100 mg/kg, p.o. and 300 mg/kg, p.o.) and B-PJ (100 mg/kg., p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, PRI, ECG patterns, levels of LDH, CK, SOD, CAT, and vascular reactivity changes. Treatment with PJ (100 mg/kg and 300 mg/kg) and B-PJ (100 mg/kg., p.o.) alone did not alter any of the parameters as compared to vehicle-treated Wistar rats. Punica granatum-treated animals showed a lesser degree of cellular infiltration in histopathological studies. CONCLUSION: Punica granatum ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of MI.

Protective effect of Solanum torvum on doxorubicin-induced nephrotoxicity in rats.

Nephrotoxicity is one of the important side effects of anthracycline antibiotics. The aim of the study was to determine the protective effect of Solanum torvum on doxorubicin-induced nephrotoxicity in rats using biochemical and histopathological approaches. Oxidative stress is the main factor in doxorubicin (DOX) induced nephrotoxicity. Wistar rats received either DOX (67.75 mg/kg, i.v, 2 days before sacrifice) or S. torvum (100mg/kg and 300 mg/kg, p.o.) prior to DOX treatment or S. torvum (100mg/kg and 300 mg/kg, p.o.) extract alone for 4 weeks. Nephrotoxicity was assessed by measuring the abnormal levels of serum creatinine and blood urea nitrogen (BUN). The anti-oxidant defence enzymes superoxide dismutase (SOD) and catalase (CAT) of kidney tissue were also measured at the end of the treatment schedule. Treatment with S. torvum (100mg/kg and 300 mg/kg) significantly (p<0.05) decreased the levels of creatinine and BUN and significantly (p<0.05) increased the anti-oxidant defence enzyme levels of SOD and CAT. Histopathological changes showed that DOX caused significant structural damages to kidneys like tubular necrosis, renal lesions and glomerular congestion which was reversed with S. torvum. The results suggest that S. torvum has the potential in preventing the nephrotoxicity induced by doxorubicin.

Effect of Solanum torvum on blood pressure and metabolic alterations in fructose hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum torvum (Solanaceae) is a plant used in Cameroon ethnomedicine for the treatment of hypertension. AIM OF THE STUDY: The present study was aimed to determine the effect of ethanolic extract of Solanum torvum (100 and 300 mg/kg; p.o. for 6 weeks) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, insulin and uric acid in fructose-induced hypertension. MATERIALS AND METHODS: The effect of ethanolic extract of Solanum torvum (100 and 300 mg/kg; p.o. for 6 weeks) on fructose (10%) induced rise in blood pressure was tested by invasive and non-invasive measurements and the biochemical parameters were studied by using standard kits. RESULTS: Ethanolic extract of Solanum torvum reduced systolic blood pressure, vascular reactivity changes to catecholamines and reversed the metabolic alterations induced by fructose. The cumulative concentration response curve (CCRC) of Angiotensin II (Ang II) using isolated strip of ascending colon was shifted towards right in rats treated with ethanolic extract of Solanum torvum. CONCLUSIONS: In conclusion, ethanolic extract of Solanum torvum could prevent the development of high blood pressure induced by a diet rich in fructose probably by reversing the metabolic alterations induced by fructose.

Caffeine withdrawal retains anticataleptic activity but Withania somnifera withdrawal potentiates haloperidol-induced catalepsy in mice.

The previous study showed that chronic treatment with Withania somnifera extract (WS) inhibited haloperidol-induced catalepsy. It is suggested that caffeine and WS may be useful adjuvants in pharmacotherapy of Parkinson's disease. There are no studies on the effect of haloperidol on mice withdrawn from caffeine or W. somnifera. We therefore studied the effect of a single administration of standardised WS containing 5.1% total withanolides (WS, 30 or 100 mg kg(-1) i.p.) and/or caffeine (3 mg kg(-1) i.p.) and withdrawal from 6 days treatment with WS and/or caffeine, on haloperidol-induced catalepsy in albino mice. Single administration of both WS and caffeine, used either alone or in combination, significantly inhibited catalepsy. Mice withdrawn from caffeine significantly inhibited haloperidol-induced catalepsy, but mice withdrawn from WS showed increased catalepsy. The study indicated that withdrawal from WS does not retain anticataleptic activity, and caffeine but not WS may be a good adjuvant in pharmacotherapy of Parkinson's disease.