Hepato-/reno-protective activity of Chinese prescription Kangen-karyu through inhibition of AGE formation and fibrosis-related protein expression in type 2 diabetes

Objectives  This study was conducted to examine whether Kangen-karyu, a Chinese prescription, has an ameliorative effect on diabetes-induced alterations such as advanced glycation endproduct (AGE) formation or the fibrotic response in liver and kidney of type 2 diabetic db/db mice. Methods  Kangen-karyu (100 or 200 mg/kg body weight/day, p.o.) was administered every day for 18 weeks to db/db mice, and its effect was compared with vehicle-treated db/db and m/m mice. Key findings  The administration of Kangen-karyu decreased the elevated serum glucose concentration in db/db mice. The increased serum creatinine and urea nitrogen levels, which reflect renal dysfunction in db/db mice, were significantly lowered by Kangen-karyu administration. The db/db mice exhibited the up-regulation of AGEs and its receptor expression in liver and kidney; however, Kangen-karyu treatment significantly reduced expression except for the receptor. Moreover, the augmented expressions of fibrosis-related proteins, transforming growth factor (TGF)-β1, fibronectin and collagen IV were down-regulated by Kangen-karyu administration. Conclusions  These results provide important evidence that Kangen-karyu exhibits a pleiotropic effect on AGE formation and fibrosis-related parameters, representing hepatoprotective and renoprotective effects against the development of diabetic complications in type 2 diabetic db/db mice.