Anti-glycative effects of oleanolic acid and ursolic acid in kidney of diabetic mice

Inhibitory effects of oleanolic acid (OA) and ursolic acid (UA) on aldose reductase (AR) and glycative products in kidney of diabetic mice were examined. OA or UA at 0.05, 0.1 or 0.2% was supplied for 10 weeks. Diabetic mice with 0.1 or 0.2% OA or UA treatments had significantly higher body weight and lower kidney weight at weeks 5 and 10 (P < 0.05). OA or UA intake at 0.1 or 0.2% increased their content in the kidney, dose-dependently decreased plasma glucose, HbA1c, renal Nε-(carboxymethyl)lysine, urinary glycated albumin and urinary albumin levels; elevated plasma insulin and renal creatinine clearance levels; as well as decreased renal sorbitol and fructose concentrations (P < 0.05). OA or UA treatments at 0.1 and 0.2% also significantly diminished renal AR activity and dose-dependently down-regulated renal AR mRNA expression (P < 0.05). These two compounds at 0.2% significantly reduced renal sorbitol dehydrogenase activity (P < 0.05). OA, not UA, treatments at 0.1 or 0.2% dose-dependently enhanced renal glyoxalase I (GLI) activity, up-regulated renal GLI mRNA expression and lowered renal methylglyoxal level (P < 0.05). Based on these marked anti-glycative effects, the supplement of OA or UA might be helpful for the prevention or alleviation of glycation associated renal diseases.