Effects of chebulic acid on advanced glycation endproducts-induced collagen cross-links

Biol Pharm Bull. 2014;37(7):1162-7. doi: 10.1248/bpb.b14-00034. Epub 2014 Apr 24.

Abstract

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 (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 ± 1.2 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/FeSO4·7H2O/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / analogs & derivatives
  • Acetaldehyde / chemistry
  • Benzopyrans / chemistry*
  • Benzopyrans / isolation & purification
  • Benzopyrans / therapeutic use
  • Biphenyl Compounds / chemistry
  • Collagen / chemistry*
  • Cross-Linking Reagents / chemistry*
  • Diabetes Complications / drug therapy
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Free Radical Scavengers / chemistry*
  • Free Radical Scavengers / isolation & purification
  • Free Radical Scavengers / therapeutic use
  • Fruit / chemistry
  • Glycation End Products, Advanced / chemistry*
  • Picrates / chemistry
  • Serum Albumin, Bovine / chemistry*
  • Terminalia / chemistry

Substances

  • Benzopyrans
  • Biphenyl Compounds
  • Cross-Linking Reagents
  • Free Radical Scavengers
  • Glycation End Products, Advanced
  • Picrates
  • chebulic acid
  • Serum Albumin, Bovine
  • Collagen
  • 1,1-diphenyl-2-picrylhydrazyl
  • Acetaldehyde
  • glycolaldehyde