Anti-obesity, antiatherogenic, anti-diabetic and antioxidant activities of J. montana ethanolic formulation in obese diabetic rats fed high-fat diet

There is a worldwide epidemic of obesity, which is associated with a number of pathologies including dyslipidemia, glucose intolerance, insulin resistance and diabetes mellitus, all of which are risk factors for cardiovascular disease and mortality. Diabetes is characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion and/or insulin action. The aim of therapy in diabetes is to achieve normoglycemia to prevent later microvascular complications (retinopathy, nephropathy, neuropathy and microangiopathy), and intensive therapy to achieve glycemic control has been shown to significantly diminish the risk of long-term complications. Since lipid abnormalities, leading to premature atherosclerosis, are the major cause of cardiovascular diseases in diabetic patients, ideal treatment for diabetes, in addition to glycemic control, should have a favorable effect on lipid profile. The five types of oral anti-diabetic drugs, currently approved for the treatment of type 2 diabetes do not have a favorable effect on cardiovascular disease, and some of these drugs are associated with serious adverse effects. Thus, new, relatively non-toxic, therapeutic agents are needed to treat hyperglycemia, which also would correct dyslipidemia to reduce the risk of cardiovascular complications of diabetes. Several FDA-approved drugs for conditions other than obesity have been investigated as treatment of excess body weight. Metformin is one such drug. Metformin, the biguanide most widely used for the treatment of type 2 diabetes mellitus, may be useful in aiding weight loss. In diabetic patients, it suppresses endogenous glucose production and may also act as an ABSTRACT J. montana extract in the form of ethanolic formulation is rich in polyphenols, monoand sesquiterpenes, Essential oils, flavonoids, tritetraand pentamethoxy quercetin derivatives. The present study was designed to investigate the antiobesity, antiatherogenic, anti-diabetic and antioxidant activities of J. montana using obese diabetic rats’ model. Rats received either regular diet, high-fat diet or high-fat diet with additional J. montana (150 and 300 mg/kg bw) for 8 weeks. In the preventive experiment, J. montana co-administered with a high fat diet significantly inhibited body weight gain, blood glucose, triglyceride, total cholesterol, LDL-C, vLDL-C, HDL-C, free fatty acid and atherogenic index levels in a dose dependent manner. J. montana-treated rats at doses of 150 and 300 mg/kg improved the insulin resistance index when compared to the high fat diet (HFD) control. Finally, the present study is designed to evaluate the effect of ethanolic extract of J. montana on figh fat diet induce obesity in rats. J. montana treatment (150 and 300 mg/kg bw) for 8 consecutive weeks prior to obese rats administration significantly prevented the decrease in the levels of hepatic oxidative stress biomarkers reduced Glutathione (GSH), Glutathione peroxidase (GPx), Glutathione reductase (GR), Superoxide dismutase (SOD) and Catalase (CAT). The J. montana extract, also exhibited its capacity to prevent the elevated thiobarbituric acid reactive substances (TBARS) in the liver tissue. In conclusion, the anti-obesity actions of J. montana are considered attributable to increased expression of energy expenditure-related fatty liver degradation, and decreased fatty acid synthesis and fat intake in the liver. Taken together, J. montana has potential as a preventive agent for type 2 diabetes mellitus (and possibly obesity) and deserves clinical trial in the near future.