INHIBITION OF α-AMYLASE AND α-GLUCOSIDASE ACTIVITY BY EPIGALLOCATECHIN-3- GALLATE (EGCG) A POLYPHENOL COMPONENT OF GREEN TEA, CAMELLIA SINENSIS AND A KNOWN HSP90 INHIBITOR

Abstract

Current diabetic therapy suffers from the adverse effects and limited pharmacologic spectrum of synthetic drugs. Starch digestive enzyme inhibitors have emerged as attractive targets in the management of hyperglycaemia but the discovery of target modulators has not been as promising. Plant derived inhibitory compounds especially polyphenols are gaining increasing scientific attention for their potential to control obesity and achieve glycaemic control while being consumed as a component of normal diet. The present study is an attempt to validate the anti-diabetic prospects of a natural source Heat shock protein 90 (Hsp90) inhibitor Epigallocatechin-3-gallate (EGCG) (a polyphenolic constituent of Camellia sinensis or green tea). Multiple modulatory effects beneficial in diabetes, cardiovascular diseases and cancer have been attributed to EGCG. However, the exact molecular mechanisms underlying these effects are still unclear. Here we have employed in vitro assays to test the direct interaction of EGCG with α-amylase and α-glucosidase that are established hyperglycaemic targets. The activity of these enzymes from different sources (pancreatic, intestinal and liver) was assayed in the presence of EGCG. Acarbose a standard anti diabetic drug was used as control. Our study showed that EGCG significantly inhibited both enzymes with greater potential for α-glucosidase inhibition. Kinetics studies predicted noncompetitive inhibition. This study lays strong evidence to anti-diabetic property of EGCG by confirming one of the many proposed mechanisms underlying its biological effects.