Phenolics from Garcinia mangostana Inhibit Advanced Glycation Endproducts Formation: Effect on Amadori Products Cross-Linked Structures and Protein Thiols

摘要

Accumulation of Advanced Glycation Endproducts (AGEs) in body tissues plays a major role in the development of diabetic complications. Here, the inhibitory effect of bioactive metabolites isolated from fruit hulls of Garcinia mangostana on AGE formation was investigated through bio-guided approach using aminoguanidine (AG) as a positive control. Including G. mangostana total methanol extract (GMT) in the reaction mixture of bovine serum albumin (BSA) and glucose or ribose inhibited the fluorescent and non-fluorescent AGEs formation in a dose dependent manner. The bioassay guided fractionation of GMT revealed isolation of four bioactive constituents from the bioactive fraction; which were identified as: garcimangosone D (>1), aromadendrin-8-C-glucopyranoside (>2), epicatechin (>3), and 2,3′,4,5′,6-pentahydroxybenzophenone (>4). All the tested compounds significantly inhibited fluorescent and non-fluorescent AGEs formation in a dose dependent manner whereas compound >3 (epicatechin) was found to be the most potent. In search for the level of action, addition of GMT, and compounds >2–>4 inhibited fructosamine (Amadori product) and protein aggregation formation in both glucose and ribose. To explore the mechanism of action, it was found that addition of GMT and only compound (>3) to reaction mixture increased protein thiol in both glucose and ribose while compounds >1, >2 and >4 only increased thiol in case of ribose. In conclusion, phenolic compounds >1–>4 inhibited AGEs formation at the levels of Amadori product and protein aggregation formation through saving protein thiol.