Studies on the Inhibitory Effect of Various Phytochemical Components on 3-Hydroxy 3-Methyl Glutaryl (HMG) CoA Reductase in Cholesterol Biosynthesis

An increased risk of morbidity and mortality in atherosclerotic diseases (angina, heart attack, peripheral vascular diseases etc.,) is a result of elevated plasma cholesterol, particularly low-density lipoprotein (LDL) cholesterol. In humans, most of the cholesterol biosynthesis occurs in hepatocytes. A number of medicinal plants have been used to control lipid level and to inhibit the oxidative stress and apoptosis amenable to pharmacologic intervention. Oral administration of the aqueous extracts of higher doses of decholestrate and phytoformulation 1 showed significant antihyperlipidemic effects. The extracts significantly lowered the levels of serum total cholesterol, triglycerides, VLDL and LDL and elevated the levels of HDL. A significant decrease in the levels of Lactate dehydrogenase (LDH), Aspartate Transaminase (AST) and Creatine kinase (CK-MB) compared to the hyperlipidemic control was also found. Atherogenic indices, cholesterol ratio, cardiac risk ratio (TG/HDL) and atherogenic coefficient are powerful indicators of the risk of developing cardiovascular diseases. In this study, it was observed that the extracts of decholestrate and phytoformulation 1 significantly reduced the atherogenic indices, cholesterol, TG/HDL ratios and atherogenic coefficient. Lower atherogenic index implies protection against coronary heart disease. Hypercholesterolemia along with high-cholesterol diet and oxidative stress increases the serum LDL-C resulting in the increased risk for the development of atherosclerosis. Decholestrate and phytoformulation1 were screened for free radical scavenging activities and were proved to posses potent antioxidant activities due to significantly enhanced Superoxide dismutase (SOD), Catalase (CAT), Vitamin E and Vitamin C. It also showed a suppressed lipid peroxidation as evidenced by decreased MDA levels. A significantly decreased cholesterogenesis in hepatocytes was observed by reduction in the rate of oxidation of NADPH to NADP, thereby reducing the HMG CoA activity. The results of the ...