Protective effects of rice bran oil in haloperidol-induced tardive dyskinesia and serotonergic responses in rats

Effect of administration of Rice bran oil [RBO] was evaluated on haloperidol elicited tardive dyskinesia in rats. Albino Wistar rats treated with haloperidol in drinking water at a dose of 0.2mg/kg/day and RBO by oral tubes at a dose of 0.4 mL/day for 5 weeks. Motor coordination, VCMs and 8-hydroxy-2-[di-n-propylamino] tetraline][8-OHDPAT] _syndrome were monitored. Striatal serotonin [5-hydroxytryptamine; 5-HT] and 5-hydroxyindolacetic acid [5- HIAA] levels were determined by high performance liquid chromatography [HPLC-EC]. Rats treated with haloperidol orally at a dose of for a period of 5 weeks developed VCMs, which increased progressively as the treatment continued for 5 weeks. Motor coordination impairment started after the 1[st] week and was maximally impaired after 3 weeks and gradually returned to the 1[st] week value. Co-administration of RBO prevented haloperidol_induced VCMs as well impairment of motor coordination. The intensity of 8-OH-DPAT_induced syndrome and decreased 5-HT metabolism were greater in water + haloperidol treated animals than RBO + haloperidol treated animals. The present study suggested that involvement of free radical in the development of TD and point to RBO as a possible therapeutic option to treat this hyperkinetic motor disorder

Neurochemical and behavioral effects of green tea [Camellia sinensis]: a model study

Being rich in polyphenolic compounds such as flavonoids, green tea is suggested to be a potential candidate for the treatment of obesity, stress, depression, Parkinson's and other disorders. Since serotonin has an important role in the pathophysiology of these disorders, present study was designed to monitor the effects of green tea in rats. Green tea extract was provided to the male Albino Wistar rats for 5 weeks, and effects on behaviors were monitored. Results show a decrease in food intake after 5th week but not before. An increase in locomotive activities of the animals was observed, as monitored in novel as well as in familiar environment. Anxiolytic effects were observed in elevated plus maze but not in light dark activity box. An increase in dopamine and serotonin turnover was observed. Our results suggest that beneficial effects of green tea drinking might be due to alteration of serotonin and/or dopamine metabolism. We thereby propose that in further experiments, green tea should be administered in animal model of learned helplessness and effects on the development of adaptation to stress should be monitored. Neurochemical estimations of catecholamine and indoleamine in these animal models of stress exposed to green tea would help in understanding the anxiolytic effects of green tea

Identification of sulfamoylbenzamide derivatives as selective cathepsin D inhibitors

Aspartic proteases play very important role in post translational processing of proteins and several of them are essential for organism's viability. Here we present the enzyme inhibition activities of different Sulfamoylbenzamide derivatives against two aspartic proteases cathepsin D and plasmepsin II. Cathepsin D is an aspartic protease that degrades proteins at acidic pH in the lysosomes, or extracellular matrix. It is overexpressed by epithelial breast cancer cells and hence hyper-secreted. On the other hand plasmepsin II is an essential enzyme of Plasmodium falciperum. Cathepsin D and Plasmepsin II are pivotal drug targets for treatment of breast cancer and malaria respectively. Virtual screening of Sulfamoylbenzamide compounds followed by enzyme inhibition assays revealed these compounds as selective Cathepsin D inhibitors while inactive against Plasmepsin-II. IC[50] values of five Sulfamoylbenzamide compounds tested are in range of 1.25-2.0 microM. N-[3-chlorophenyl]-2-sulfamoylbenzamide is identified as the most potent of all tested Sulfamoylbenzamide compounds with IC[50] 1.25 microM. It was also noted that the docking score of theses compounds was better in case of Cathepsin D as compared to Plasmepsin-II. Docking score ranges from -29.9 +/- 1.16 to -35.1 +/- 0.13 in case of Cathepsin D, while from -24.0 +/- 0.10 to -29.5 +/- 0.10 in case of Plasmepsin-II