Institute of Natural Medicine, University of Toyama, Sugitani, Toyama 930–0194, Japan.
Biol Pharm Bull. 2011;34(3):383-8. doi: 10.1248/bpb.34.383.
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 kangen-karyu ameliorating the development of diabetic hepatic damages via regulating oxidative stress and inflammation.
糖尿病并发症的预防和治疗被认为是糖尿病患者常规护理的重中之重。我们一直在使用一种中药方剂——康肾液进行糖尿病的临床前动物实验,以检验其治疗潜力。在本研究中,我们进一步研究了康肾液的抗糖尿病机制,特别是其对 db/db 小鼠高血糖诱导的肝氧化应激和炎症的调节作用。康肾液(100 或 200mg/kg 体重/天,口服(p.o.),每天给药 18 周,与 vehicle 处理的 db/db 和 m/m 小鼠进行比较。康肾液的给药降低了 db/db 小鼠升高的血清和肝葡萄糖浓度。康肾液处理后,p22(phox)和 Nox-4 蛋白(还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶亚基)的升高表达显著降低。肝组织中与氧化应激相关的标志物(活性氧、还原型谷胱甘肽/氧化型谷胱甘肽比值和硫代巴比妥酸反应物质)也因康肾液处理而得到显著改善。db/db 小鼠肝脏中核因子-κBp65、环氧化酶-2 和诱导型一氧化氮合酶水平上调,但康肾液处理显著降低了这些表达。综上所述,我们的研究结果支持康肾液通过调节氧化应激和炎症改善糖尿病肝损伤的治疗证据。