TETRAHYDROXYSTILBENE GLUCOSIDE RETARDS PROGRESSION OF DIABETIC CARDIOMYOPATHY THROUGH MODULATIONS OF OXIDATIVE STRESS, PROINFLAMMATORY CYTOKINES, AND AMP-ACTIVATED PROTEIN KINASE

Objectives Diabetic patients are known to have an independent risk of cardiomyopathy. Hyperglycemia leads to upregulation of reactive oxygen species (ROS) and inflammatory condition that may contribute to diabetic cardiomyopathy. There are evidences that the activation of AMPK is playing pivotal role in the lipid and glucose metabolism. 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) from Polygoni multiflori has been demonstrated to possess a variety of pharmacological activities, including antioxidant, anti-inflammatory and anti-atherosclerotic effect. The present study was sought to investigate the effect of TSG on modulating diabetic cardiomyopathy and the mechanisms involved. Methods A high-fat diet and low-dose streptozotocin administration were used to induce type 2 diabetes in Wistar rats. Diabetic rats were treated with TSG for 16 weeks. At the end of this study, after cardiac function measurements were performed, rats were sacrificed and their hearts were harvested for further histologic and molecular biologic analysis. Cardiac tissue was analysed by ELISA for the protein content of the cytokines TNF-alpha, IL-6, IL-1beta, and TGF-beta. Phosphorylation of AMP was analysed by western blot, and the total cardiac collagen content was analysed by Sirius red staining. Results Results showed that the levels of nitric oxide (NO) and superoxide dismutase (SOD) activity in plasma and myocardium in TSG-treated group were significantly higher than those in diabetic control group. The levels of malondialdehyde (MDA) in plasma and myocardium in TSG-treated group were significantly lower than those in diabetic control group. Hyperglycemia markedly enhanced cardiac production of proinflammatory cytokine IL-1 beta. TSG reduced IL-1 beta but increased TNF-alpha and IL-6 levels in the diabetic cardiomyopathy. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic cardiac tissues. In contrast, TSG treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group Conclusions These findings indicate that the protective mechanisms of TSG on diabetic cardiomyopathy are involved in the alleviation of oxidative stress injury and regulating proinflammatory cytokines, partially via activation of AMPK protein. Acknowledgements This work was supported by the National Nature Science Foundation of China (NSFC) Grant 81000576 to Fei Cai, Natural Science Foundation of Hubei Province of China 2011CDB315 to Shou-yi Gan.