Abstract
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.
Highlights
On a long term basis, the diabetic’s health condition is complicated by repeated blood glucose level elevations
Incubation of bovine serum albumin (BSA) with glucose or ribose for four weeks significantly increased the formation of fluorescent (Figure 1) and non-fluorescent (CML) Advanced Glycation Endproducts (AGEs) compared with the corresponding blank (Figure 2)
G. mangostana was evaluated for its inhibitory effects against two monosaccharide-mediated protein glycation reactions and oxidative damage of BSA
Summary
On a long term basis, the diabetic’s health condition is complicated by repeated blood glucose level elevations. The carbonyl groups of glucose react non-enzymatically with proteins resulting in the formation of structures called Schiff’s bases. This is followed by rearrangement to produce Amadori products like fructosamine [1]. Herbal drugs are widely used all over the world due to their high efficacy, fewer side effects and relatively low cost. In this regard, some plant extracts have been evaluated for their effects on the formation of AGEs [10,11,12,13]. As free radicals are involved in the formation of AGEs, it is reasonable to assume that phenolic antioxidants can inhibit the formation of AGEs [14]
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