SCREENING AND EVALUATION OF SELECTED HERBAL EXTRACT FOR MANAGEMENT OF OBESITY AND ASSOCIATED METABOLIC DISORDERS
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Date
2015-12-30
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COLLEGE OF VETERINARY AND ANIMAL SCIENCES MANNUTHY, THRISSUR
Abstract
The 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.
Description
Submitted in partial fulfilment of the requirement for the degree of
Doctor of Philosophy in Veterinary Pharmacology and Toxicology