Chinese prescription Kangen-karyu ameliorates the development of diabetic hepatic damages via regulating oxidative stress and inflammation in the liver of db/db mice

Abstract

The prevention and treatment of diabetic complications are considered to be the most important for the general care of diabetic patients. We have been conducting pre-clinical animal experiments related to diabetes using Kangen-karyu, a Chinese prescription, to examine its therapeutic potential. In the present study, we further studied the anti-diabetic mechanism of Kangen-karyu, especially on the regulation of hyperglycemia-induced hepatic oxidative stress and inflammation in db/db mice. Kangen-karyu (100 or 200 mg/kg body weight/day, per os (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 and hepatic glucose concentration in db/db mice. The elevated expressions of p22 phox and Nox-4 proteins (reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits) were significantly decreased after Kangen-karyu treatments. The oxidative stress-related markers in hepatic tissue (reactive oxygen species, reduced glutathione/oxidized glutathione ratio, and thiobarbituric acid-reactive substance) were also significantly ameliorated by the Kangen-karyu treatments. The db/db mice exhibited the up-regulation of nuclear factor-κBp65, cyclooxygenase-2, and inducible nitric oxide synthase levels in the liver; however, Kangen-karyu treatment significantly reduced those expressions. Taking these into consideration, our findings support the therapeutic evidence for Kangenkaryu ameliorating the development of diabetic hepatic damages via regulating oxidative stress and inflammation. © 2011 Pharmaceutical Society of Japan.