Hypoglycemic and hypolipidemic effects of Garcinia cambogia extracts in streptozotocin-nicotinamide induced diabetic rat model.

BACKGROUND AND OBJECTIVES: Diabetes mellitus, a global health problem, is associated with metabolic complications such as hyperglycemia, hyperlipidemia, hypertension, cardiovascular diseases, and loss of vision. The present study evaluated the antidiabetic and antihyperlipidemic effects of ethanol extract of Garcinia cambogia (L.) N. Robson (G. cambogia) fruit rind in a streptozotocin-nicotinamide induced diabetic Wistar Rat model. MATERIALS AND METHODS: Streptozotocin-nicotinamide was injected intraperitoneally to induce diabetes in Wistar rats. Five groups of rats (n=6) - normal control, diabetic, diabetic treated with G. cambogia at 400 mg/kg and 800 mg/kg body weight, and diabetic treated with metformin at 500 mg/kg body weight, were studied. Blood samples were collected after three weeks of treatment. Random blood glucose (RBG), Serum total cholesterol levels (TCL), serum total triglyceride levels (TGL), high-density lipoprotein levels, and body weight were measured. RESULTS: Although G. cambogia treatment did not have any antidiabetic activity (p>0.05) rind in the streptozotocin-nicotinamide induced diabetic Wistar Rat model, it decreased the serum TCL, and body weight significantly (P<0.05). CONCLUSIONS: Ethanolic extract of G. cambogia fruit rind possesses anti-obesity activity and significantly reduces total cholesterol but does not have antidiabetic activity.

Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice.

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects.

Co-administration of haloperidol and drugs affecting the angiotensin pathway: effect on the extrapyramidal system.

The present study investigates the extrapyramidal effects of co-administration of enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin receptor blocker) with haloperidol in mice. Enalapril/losartan (as a suspension in 1% gum acacia) was administered by oral gavage and haloperidol was administered as an intraperitoneal injection to all the animals for seven days. Catalepsy was measured 30 min after the administration of haloperidol (1 mg/kg i.p.) on days 1 and 7. Observations on day 1 constituted the acute study (single dose administration) and observations on day 7, constituted the chronic study (repeated dose administration). Both acute and chronic administration of enalapril/losartan produced an increase in the duration of haloperidol induced catalepsy at the highest dose (20 mg/kg). Enalapril produced a more pronounced increase in the duration of catalepsy as compared to losartan on both acute and chronic administration. Results of our study suggest that co-administration of anti-psychotics and drugs affecting the angiotensin system can lead to an increase in motor side effects and therefore should be used with caution in patients with these co-morbid conditions.

Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats.

The present study investigates the anxiolytic activity of NR-ANX-C, a standardized polyherbal formulation containing the extracts of Withania somnifera, Ocimum sanctum, Camellia sinensis, Triphala, and Shilajit in ethanol withdrawal- (EW-) induced anxiety behavior in rats. Ethanol dependence in rats was produced by substitution of drinking water with 7.5% v/v alcohol for 10 days. Then, ethanol withdrawal was induced by replacing alcohol with drinking water, 12 hours prior to experimentation. After confirming induction of withdrawal symptoms in the alcohol deprived animals, the anxiolytic activity of the test compound in graded doses (10, 20, and 40 mg/kg) was compared to the standard drug alprazolam (0.08 mg/kg) in the elevated plus maze and bright and dark arena paradigms. In our study, single and repeated dose administration of NR-ANX-C reduced EW-induced anxiety in a dose-dependent manner. Even though the anxiolytic activity was not significant at lower doses, NR-ANX-C at the highest dose tested (40 mg/kg) produced significant anxiolytic activity that was comparable to the standard drug alprazolam. Based on our findings we believe that NR-ANX-C has the potential to be used as an alternative to benzodiazepines in the treatment of EW-induced anxiety.

Evaluation of the anti-ulcer activity of NR-ANX-C (a polyherbal formulation) in aspirin & pyloric ligature induced gastric ulcers in albino rats.

BACKGROUND & OBJECTIVES: The aetiology of gastric ulcers is not completely understood and continuous use of anti-ulcer agents leads to many side effects. In this study we evaluated the anti-ulcer efficacy of a polyherbal formulation with potent antioxidant activity in aspirin and pyloric ligature induced gastric ulcers in rats. METHODS: The efficacy of the polyherbal formulation NR-ANX-C (composed of the extracts from Withania somnifera, Camellia sinensis, Ocimum sanctum, shilajith and triphala) was evaluated in terms of antioxidant potential as assessed in terms of protection from lipid peroxidation and the antiulcer activity as seen by the area of gastric lesions, gastric juice volume, gastric pH, total acidity and total adherent gastric mucus content. RESULTS: In our study, NR-ANX-C (25 and 50 mg/kg) was more efficacious than ranitidine in reducing ulcer index in both the models. At the highest dose tested (50 mg/kg), NR-ANX-C was comparable to omeprazole in preventing ulcer formation in the pyloric ligature model. NR-ANX-C showed a dose- dependent decrease in gastric juice volume and total acidity in both the models. A dose-dependent increase in gastric pH and total adherent gastric mucus was also seen in NR-ANX-C treated groups. The extent of lipid peroxidation was also reduced in the test drug treated groups. INTERPRETATION & CONCLUSION: Based on our findings, we presume that the cytoprotective, anti-secretary and antioxidant properties of NR-ANX-C were responsible for its anti-ulcer activity. These findings suggest the potential for use of NR-ANX-C as an adjuvant in the treatment of gastric ulcer.

Effect of Withania somnifera root extract on haloperidol-induced catalepsy in albino mice.

The objective of the study was to evaluate the anticataleptic effect of Withania somnifera (WS) extract, on haloperidol-induced catalepsy in albino mice. Catalepsy was induced with haloperidol (1 mg/kg) i.p. in five groups of male albino mice (n = 6). Three groups received Withania somnifera extract (1.7, 4.25, 8.5 mg/kg) respectively, one group received scopolamine (1 mg/kg) and one group received the vehicle (1% gum acacia) orally, 30 min prior to haloperidol administration. Catalepsy was measured by using standard bar test at 30, 60, 90, 120 and 240 min. This constituted the acute study. For the chronic study, the drugs were administered for 6 more days. Catalepsy was again measured on day 7. Animals were then sacrificed by cervical dislocation and superoxide dismutase (SOD) activity was estimated in the brain. In this study, Withania somnifera extract treated groups showed a dose dependent reduction in cataleptic scores, both in the acute and chronic study. The SOD activity in brain was also found to be lowered in the WS (4.25 mg, 8.5 mg/kg) treated groups. In conclusion, Withania somnifera was found to be more efficacious than scopolamine in reversing haloperidol induced catalepsy. A clear correlation between the SOD levels and cataleptic scores was observed. We believe that the antioxidant properties of this drug could have contributed to the anticataleptic effect.

Effect of NR-ANX-C (a polyherbal formulation) on haloperidol induced catalepsy in albino mice.

BACKGROUND & OBJECTIVE: Use of typical antipsychotics like haloperidol in treatment of schizophrenia is associated with a high incidence of extrapyramidal side effects. In rodents, administration of haloperidol leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we evaluated the anticataleptic efficacy of NR-ANX-C, a polyherbal formulation containing bioactives of Withania somnifera, Ocimum sanctum, Camellia sinensis, triphala and shilajit in haloperidol induced catalepsy in mice. METHODS: Five groups (n = 6) of male albino mice were used in the study. Catalepsy was induced by ip administration of haloperidol (1mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of NR-ANX-C (10, 25 and 50 mg/kg) with scopolamine (1 mg/kg). The superoxide dismutase (SOD) level in brain tissue was also estimated to correlate the levels of oxidative stress and degree of catalepsy in the animal. RESULTS: Significant (P<0.01) reduction in the cataleptic scores was observed in all NR-ANX-C treated groups and maximum reduction was observed in the NR-ANX-C (25 mg/kg) treated group. Significant (P<0.05) reduction in SOD activity was observed in NR-ANX-C (25 and 50 mg/kg) treated groups and maximum reduction was observed in NR-ANX-C (25mg/kg) treated group. INTERPRETATION & CONCLUSION: In our study, maximum reduction in cataleptic score was observed in NR-ANX-C (25 mg/kg) treated group. The maximum reduction in SOD activity was also observed in the same group. These findings suggest a possible involvement of the antioxidant potential of NRANX- C in alleviating haloperidol induced catalepsy.

Synthesis of some new biologically active bis-(thiadiazolotriazines) and bis-(thiadiazolotriazinyl) alkanes.

4-Amino-3-mercapto-1,2,4-triazin-5(4H)-ones (1) were condensed with dicarboxylic acids 2 to yield bis-(4-oxo-4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-7-yl)alkanes (3b-d,f-h,j-l,n-p) and bis-thiadiazolotriazines (3a,e,i,m). All the newly synthesised compounds were characterised by analytical, IR, NMR and mass spectral studies. Some of the newly synthesised compounds were screened for their antibacterial and antifungal properties. Among the tested compounds, compound 7,7'-(1,4-butanediyl)-his-(3-t-butyl-4-oxo-4H-1,3,4-thia-diazolo[2,3-c]-1,2,4-triazine (3p) exhibited highest degree of antifungal activity.

Effect of propranolol and nifedipine on maximal electroshock-induced seizures in mice: individually and in combination.

A comparative effect of propranolol and nifedipine administered individually and in combination at graded dose levels; and that of phenytoin at 30 mg kg-1 on maximal electroshock (MES)-induced seizure in mice was investigated. Propranolol in doses of 10 mg kg-1 and 20 mg kg-1, and nifedipine in doses of 8 mg kg-1 and 16 mg kg-1 significantly modified MES activity. Propranolol (40 mg kg-1), and a combination of propranolol (20 mg kg-1) and nifedipine (8 mg kg-1), produced antiMES activity, which was comparable to that of phenytoin (30 mg kg-1). In mice treated with propranolol and nifedipine combination, the tonic flexor and tonic extensor phase ratios (F/E ratio) were significantly higher than individual drug responses. Our findings suggest that a combination of propranolol and nifedipine has either synergistic or an additive effect in controlling MES-induced seizures in mice.