INHIBITION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME A (HMG Co-A) REDUCTASE IN LIVER MICROSOMES BY MORINGA OLEIFERA L. POLYPHENOLS

Phytochemicals are the bioactive components present at micro level in our daily diet, especially the phenolic antioxidants, contribute to the prevention of cardiovascular and other degenerative diseases. Moringa oleifera (MO) leaves polyphenols effect on the activity of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG CoA) reductase was studied using a spectrophotometric assay based on the stoichiometric formation of coenzyme A (SH) during the reduction of microsomal HMG CoA to mevalonate at different concentrations (200400 μg). Activity of HMGCoA reductase was inhibited by MO polyphenols significantly (p<0.05) at the concentrations studied. The Coenzyme A released at the end of assay in the control was higher (18.87±0.12 n Moles) significantly than the MO polyphenol extract, which was dose dependent (14.69±0.07 to 10.26±0.33 n Moles). The results reveal the potency of the MO polyphenols in inhibiting the HMGCoA reductase. Hence, the MO polyphenols can be explored for its role as a cholesterol lowering agent. INTRODUCTION: Elevated plasma cholesterol concentration is a well known risk factor for the development of atherosclerosis and coronary heart disease (CHD). Consequently, public health recommendations are aimed at reducing plasma cholesterol concentration . In humans, most cholesterol biosynthesis occurs in the liver. The enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMG CoA reductase; E.C 1.1.1.34) is responsible for catalysing the NADPH-dependent, twostep reduction of HMG-CoA to mevalonate. This reaction is a highly regulated process within the cholesterol biosynthetic pathway, and so is an attractive target for intervention in the treatment of hypercholesterolaemia. HMG CoA Reductase is found in cytosol and microsomal fractions of the cell . Inhibition of HMG CoA reductase prevents and reverses MYC-induced lymphomagenesis, treats adenocarcinomas of the prostate, stomach, lung, breast and colon and Ewing's sarcomas, promotes antiinflammatory pathways in vascular wall 3 and inhibits cholesterol biosynthesis . Several inhibitors of HMGCoA reductase have been developed as cholesterollowering therapeutic agents known as statins, fibrates, niacin etc . Medicinal plants and their extracts have gained increasing importance over the past years, since they can be used as sources of herbal drugs .