Effects of cyanidin-3-rutinoside on methylglyoxal-induced protein glycation, oxidative DNA damage and vascular abnormalities

Abstract

Protein glycation is a non-enzymatic reaction between reducing sugars or dicarbonyl compounds (such as methylglyoxal) with protein causing the formation of advanced glycation end products (AGEs) linked to the development of diabetic vascular complications. Cyanidin-3-rutinoside (C3R), a natural anthocyanin present in fruits and vegetables, possesses various pharmacological activities. The objectives of the present study were to investigate the anti-glycation and cardioprotective effect of C3R in in vitro and in animal model. The results showed that C3R (0.125-1 mM) markedly inhibited fluorescent and non-fluorescent AGEs formation, fructosamine formation, protein carbonyl formation, protein thiol groups depletion and β-amyloid cross structure formation in bovine serum albumin (BSA) induced by ribose, fructose, glucose, galactose or methylglyoxal. C3R directly trapped methylglyoxal and scavenged superoxide anion and hydroxyl radicals-induced oxidative DNA fragmentation during methylglyoxal/lysine reaction. Moreover, C3R (3 µM) prevented methylglyoxal-induced vascular abnormalities in isolated rat thoracic aorta and mesenteric arterial bed by normalizing vascular functions (contraction and relaxation). In feeding studies, C3R treatment (30 and 100 mg/kg/day) decreased the accumulation of plasma methylglyoxal after 8 weeks of feeding period with methylglyoxal (60-120 mg/day). In addition, C3R also attenuated methylglyoxal-impaired vascular functions through normalizing contraction and relaxation as well as upregulating endothelial nitric oxide synthase (eNOS) mRNA and decreasing AGEs accumulation in aortic tissue. The present study demonstrated that C3R could be a potential compound for preventing methylglyoxal-mediated diabetic vascular complications.