Synthesis, computational studies and preliminary pharmacological evaluation of 2-[4-(aryl substituted) piperazin-1-yl] N, N-diphenylacetamides as potential antipsychotics.

A series of 2-[4-(aryl substituted) piperazin-1-yl] N, N-diphenylacetamides have been synthesized and the target compounds (3a-j) were evaluated for atypical antipsychotic activity in apomorphine induced climbing, 5-HTP induced head twitches behavior and catalepsy studies in mice. The physicochemical similarity of the target compounds with respect to standard drugs clozapine, ketanserin and risperidone was calculated by using software programs. Among them, compound 3e showed maximum atypical antipsychotic like profile.

Bcl-2 expression alters the mitochondrial tri carboxyl Acid pathway in hepatic ischemic and reperfusion induced necrosis and apoptosis in rat liver.

Ischemic and reperfusion injury leads to necrosis and apoptosis. Mitochondrial enzymes and antiapoptotic gene plays an important role in necrosis and apoptosis. The aim of this study was to investigate the role of Bcl-2 expression in alternations in mitochondrial energy regulation during hepatic ischemia and reperfusion and role in necrosis and apoptosis. Total 12 Wistar rats were divided into sham-operated control group (I) and ischemia and reperfusion group (II). Mitochondrial tri carboxylic acid cycles marker enzymes, respiratory marker enzymes, apoptotic cells, necrotic cells and Bcl-2 expression was measured. Number of necrotic and apoptotic cells were increased in ischemic and reperfusion group with reducing tri carboxylic acid cycles marker enzymes, respiratory marker enzymes and decreasing of Bcl-2 expression. On the basis of our findings it may be concluded that suppression of Bcl-2 gene, inhibition of tri carboxylic acid cycles and respiration rate, adenosine tri phosphate production in mitochondria is a pathophysiological consequences which provides a clue for necrosis and apoptosis in hepatic ischemic and reperfusion injury.

Attenuation of mitochondrial injury by L-arginine preconditioning of the liver.

The present study was aimed to evaluate the efficacy of L-arginine on mitochondrial function in ischemic and reperfusion (I/R) induced hepatic injury. Adult Wistar rat were subjected to 1 h of partial liver ischemia followed by 3 hour reperfusion. Eighteen wistar rats were divided into three groups viz. sham-operated control group (I) (n=6), ischemia and reperfusion (I/R) group (II) (n=6), L-arginine treated group (100 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n=6). Mitochondrial injury was assessed in terms of decreased (P<0.05) activities of mitochondrial antioxidant enzymes (GSH, SOD, CAT), respiratory marker enzymes (NADH dehydrogenase, cytochrome c oxidases) and hepatocytes nitric oxide production. Pre-treatment with L-arginine (10 mg/kg/p.o. for 7 days) significantly counteracted the alternations of hepatic enzymes and mitochondrial respiratory and antioxidant enzymes. In addition, electron microscopy and histopathology study showed the restoration of cellular normalcy and accredits the cytoprotective role of L-arginine against I/R induced hepatocellular injury. On the basis of these findings it may be concluded that L-arginine protects mitochondrial function in hepatic ischemic and reperfused liver.

Hypolipidemic activity of aqueous extract of Withania coagulans Dunal in albino rats.

Administration of an aqueous extract of fruits of Withania coagulans (1 g/kg; p.o.) to high fat diet induced hyperlipidemic rats for 7 weeks, significantly reduced elevated serum cholesterol, triglycerides and lipoprotein levels. This drug also showed hypolipidemic activity in triton induced hypercholesterolemia. The histopathological examination of liver tissues of treated hyperlipidemic rats showed comparatively lesser degenerative changes compared with hyperlipidemic controls. The hypolipidemic effect of W. coagulans fruits was found to be comparable to that of an Ayurvedic product containing Commiphora mukkul.

Hypoglycemic activity of Withania coagulans Dunal in streptozotocin induced diabetic rats.

Administration of aqueous extract of fruits of Withania coagulans Dunal significantly lowered the blood sugar, serum cholesterol, serum LPO, and hepatic LPO levels at the highest concentration of 1g/kg; p.o. in streptozotocin induced diabetic rats. In normal rats as well the blood sugar levels were significantly decreased following treatment with the above drug. Withania coagulans also exhibited free radical scavenging activity in an in vitro system using DPPH.