Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats

Biochem Pharmacol. 1998 Dec 15;56(12):1607-14. doi: 10.1016/s0006-2952(98)00237-8.


A close association between increased oxidative stress and hyperglycemia has been postulated to contribute significantly to the accelerated accumulation of advanced glycation end products (AGEs) and the cross-linking of collagen in diabetes mellitus. In the present work, we report the influence of curcumin, an efficient antioxidant, on the level of AGEs and the cross-linking of collagen in diabetic rats. Diabetic rats were given curcumin (200 mg/kg body wt) orally for a duration of 8 weeks. The antioxidant status in serum and the level of AGEs, cross-linking and browning of collagen in tail tendons and skin were investigated. The oxidative stress observed in diabetic rats was reduced significantly by curcumin administration. Nonenzymic antioxidants such as vitamin C, vitamin E, and glutathione were maintained at near normal values in curcumin-treated diabetic animals. Similarly, the accumulation of lipid peroxidation products in diabetic serum was reduced significantly by curcumin. Accelerated accumulation of AGE-collagen in diabetic animals, as detected by ELISA, was prevented by curcumin. Extensive cross-linking of collagen in the tail tendon and skin of diabetic animals was also prevented to a greater extent by curcumin treatment. A correlation between the level of AGEs and collagen cross-linking was noted, suggesting the involvement of advanced glycation in cross-linking. It was also noted that the preventive effect of curcumin on the advanced glycation and cross-linking of collagen was more pronounced than its therapeutic effect. However, the Maillard reaction fluorescence in both tail and skin collagen remained unaltered by curcumin. This study confirms the significance of free radicals in the accumulation of AGEs and cross-linking of collagen in diabetes. It supports curcumin administration for the prevention of AGE-induced complications of diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antioxidants / analysis
  • Antioxidants / therapeutic use*
  • Collagen / chemistry
  • Collagen / immunology
  • Collagen / metabolism*
  • Curcumin / therapeutic use*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Glycation End Products, Advanced / chemistry
  • Glycation End Products, Advanced / immunology
  • Glycation End Products, Advanced / metabolism*
  • Lipid Peroxidation
  • Male
  • Rats
  • Rats, Wistar
  • Ribonucleases / immunology
  • Skin / metabolism
  • Tendons / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Glycation End Products, Advanced
  • Collagen
  • Ribonucleases
  • Curcumin