Usha P.T.A.J. JOSHUA ALLAN2023-01-092023-01-092015-12-30https://krishikosh.egranth.ac.in/handle/1/5810191563Submitted in partial fulfilment of the requirement for the degree of Doctor of Philosophy in Veterinary Pharmacology and ToxicologyThe global prevalence of obesity and its associated metabolic comorbidities, especially dyslipidemia are at present escalating alarmingly, which necessitates urgent implementation of earnest preventive and therapeutic measures. Identifying the medications that target obesity, dyslipidemia and the underlying oxidative stress with less or negligible side effects, hence seem to be an excellent strategy. The present study was undertaken to identify a safe herbal substance possessing anti-obese and anti-dyslipidemic potentials along with targeting the underlying oxidative stress. The plants were shortlisted based on history of food use, usage in daily life, mentioned in texts of Ayurveda for medicinal use, not classified as endangered species and present in normally traded as commodities list. Accordingly, six plant extracts were initially screened for acute oral toxicity and hypotriglyceridemic effect in oral lipid load test. The screening tests indicated aqueous extract of Zingiber officinale rhizome as the safe and potent extract, which was further fractionated to improve the solubility. The fraction showing highest solubility i.e., water soluble fraction of Zingiber officinale extract (WFZE) was further subjected to acute oral toxicity and oral lipid load tests to ensure the safety and efficacy. The WFZE was found to be safe upto 5000 mg/kg body weight in acute oral toxicity study in rat and its triglyceride lowering activity was found to be better than the parent extract. Consequently, WFZE was evaluated for anti-obese and anti-dyslipidemic potentials. The anti-obesity effect of WFZE was established in high fat diet induced obese male rats by the significant reduction in body weight gain, adiposity and triglyceride levels along with the amelioration of metabolic perturbations such as hyperleptinemia, increase in the FFA, glucose and insulin. Moreover, the total hepatic lipids, serum AST and ALT were reduced while atherogenic index and insulin resistance indices such as HOMA and QUIKI were controlled and the severity of histopathological lesions in liver, pancreas and adipose tissue were reduced after treatment with WFZE. In addition, WFZE treatment significantly reduced the oxidative stress induced by high fat feeding as evident from the significant decrease in hepatic MDA and increase in SOD, catalase and glutathione reductase levels, indicating the anti-oxidant potential of WFZE. The anti-dyslipidemic activity of WFZE was further demonstrated in Triton WR-1339 induced and cholesterol cholic acid induced dyslipidemic models. A significant reduction in serum triglycerides and cholesterol levels following the administration of Triton WR-1339 and chronic feeding of cholesterol and cholic acid in rats established the anti-dyslipidemic activity of WFZE. To elucidate the mechanism of action, WFZE was investigated for its activity against pancreatic lipase, which indicated promising pancreatic lipase inhibitory activity in vitro. The findings of the present study suggest that WFZE is a safe, effective therapeutic agent for the management of obesity and dyslipidemia acting via the inhibition of pancreatic lipase and anti-oxidant mechanisms.EnglishThesis