Renoprotective effect of Kangen-karyu on the development of diabetic nephropathy in type 2 diabetic db/db mice

The present study was conducted to examine whether Kangen-karyu, a Chinese prescription, has an ameliorative effect on diabetes-induced alterations such as oxidative stress, apoptosis, inflammation, and/or morphological changes in the kidney of type 2 diabetic db/db mice. 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. The administration of Kangen-karyu decreased the elevated serum glucose concentration in db/db mice, and reduced the increased oxidative biomarkers including the generation of reactive oxygen species and lipid peroxidation in the serum and kidney. The increased serum creatinine and urea nitrogen levels, which reflect renal dysfunction, and renal structural changes, representing glomerular enlargement, in db/db mice were significantly lowered by Kangen-karyu administration. The db/db mice exhibited the up-regulation of nicotinamide adenine dinucleotide phosphate oxidase subunits, nuclear factor-kappaB, cyclooxygenase-2, and inducible nitric oxide synthase levels in the kidney; however, Kangen-karyu treatment significantly reduced those expressions. Moreover, the augmented expressions of apoptosis-related proteins, cytochrome c and Bax, were down-regulated by Kangen-karyu administration. Taken together, these results provide important evidence that Kangen-karyu exhibited a pleiotropic effect on several oxidative stress-related parameters and exerted a renoprotective effect on the development of diabetic nephropathy in type 2 diabetic db/db mice.