Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
Free Radic Res. 2011 Jul;45(7):788-95. doi: 10.3109/10715762.2011.579121. Epub 2011 May 9.
Oxidative stress has been strongly implicated in the pathogenesis of diabetic encephalopathy (DE). Numerous studies have demonstrated a close relationship between oxidative stress and AMPK activation in various disorders, including diabetes-related brain disorders. Since curcumin has powerful antioxidant properties, this study investigated its effects on hyperglycaemia-mediated oxidative stress and AMPK activation in rats with DE. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ-55 mg/kg BW). The diabetic rats were then orally administered curcumin (100 mg/kg BW) or vehicle for 8 weeks. The cerebra of the diabetic rats displayed upregulated protein expression of AdipoR1, p-AMPKα1, Tak1, GLUT4, NADPH oxidase sub-units, caspase-12 and 3-NT and increased lipid peroxidation in comparison with the controls and all of these effects were significantly attenuated with curcumin treatment, except for the increase in AdipoR1 expressions. These results provide a new insight into the beneficial effects of curcumin on hyperglycaemia-mediated DE, which are produced through the down-regulation of AMPK-mediated gluconeogenesis associated with its anti-oxidant property.
氧化应激在糖尿病性脑病(DE)的发病机制中起着重要作用。许多研究表明,氧化应激与 AMPK 激活之间存在密切关系,包括与糖尿病相关的脑疾病。由于姜黄素具有强大的抗氧化特性,本研究探讨了其对 DE 大鼠高血糖介导的氧化应激和 AMPK 激活的影响。糖尿病通过单次腹腔注射链脲佐菌素(STZ-55mg/kgBW)诱导。然后,糖尿病大鼠口服给予姜黄素(100mg/kgBW)或载体 8 周。与对照组相比,糖尿病大鼠的大脑中 AdipoR1、p-AMPKα1、Tak1、GLUT4、NADPH 氧化酶亚基、caspase-12 和 3-NT 的蛋白表达上调,脂质过氧化增加,而这些效应均被姜黄素治疗显著减弱,除了 AdipoR1 的表达增加。这些结果为姜黄素对高血糖介导的 DE 的有益作用提供了新的见解,这些作用是通过下调 AMPK 介导的与抗氧化特性相关的糖异生产生的。