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 μM. Also, the breaking activity on collagen cross-links induced by glycol-BSA was potent with CA (IC ₅₀=1.46±0.05 mM), exhibiting 50-fold stronger breaking activity than with ALT-711, a well-known cross-link breaker (IC ₅₀=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±1.2 μg 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 · 7H ₂O/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.