Effects of Chebulic Acid on Advanced Glycation Endproducts-Induced Collagen Cross-Links

Advanced glycation end-products (AGEs) have been implicated in the development of diabetic complications. We report the antiglycating activity of chebulic acid (CA), isolated from Terminalia chebula on breaking the cross-links of proteins induced by AGEs and inhibiting the formation of AGEs. Aminoguanidine (AG) reduced 50% of glycated bovine serum albumin (BSA) with glycolaldehyde (glycol-BSA)-induced cross-links of collagen at a concentration of 67.8 +/- 2.5 mM, the level of CA required for exerting a similar antiglycating activity was 38.8 +/- 0.5 mu M. Also, the breaking activity on collagen cross-links induced by glycol-BSA was potent with CA (IC50=1.46 +/- 0.05 mM), exhibiting 50-fold stronger breaking activity than with ALT-711, a well-known cross-link breaker (IC50=72.2 +/- 2.4 mM). IC50 values of DPPH. scavenging activity for CA and ascorbic acid (AA) were 39.2 +/- 4.9 and 19.0 +/- 1.29 mu g dry matter (DM) mL(-1), respectively, and ferric reducing and antioxidant power (FRAP) activities for CA and AA were 4.70 +/- 0.06 and 11.4 +/- 0.1 mmol/FeSO4 center dot 7H(2)O/g DM, respectively. The chelating activities of CA, AG and ALT711 on copper-catalyzed oxidation of AA were compared, and in increasing order, ALT-711 (IC50 of 1.92 +/- 0.20 mM)<CA (IC50 of 0.96 +/- 0.07 mM)<AG (0.47 +/- 0.05 mM). Thus, CA could be a breaker as well as an inhibitor of AGE cross-linking, the activity of which may be explained in large part by its chelating and antioxidant activities, suggesting that CA may constitute a promising antiglycating candidate in intervening AGE-mediated diabetic complications.