Reduced HMGB 1-Mediated Pathway and Oxidative Stress in Resveratrol-Treated Diabetic Mice: A Possible Mechanism of Cardioprotection of Resveratrol in Diabetes Mellitus.

ABSTRACT

Myocardial fibrosis and inflammation are intricately linked in diabetic cardiomyopathy (DCM), and resveratrol has been shown to attenuate oxidative stress, inflammation, and fibrosis in several cell types or animal models. High mobility group box 1 (HMGB 1), a proinflammatory cytokine, has been reported to regulate fibrosis and inflammation in various organs. Then the present study aimed to reveal the expression of HMGB 1-mediated signaling pathway and oxidative stress in resveratrol-treated diabetic mice. The significant increase in serum HMGB 1 concentration in diabetic mice was attenuated by treatment with resveratrol. Similarly, western blot analysis revealed a significant increase of HMGB 1 protein in monocytes and heart tissues of diabetic mice, and resveratrol partly normalized the changes. In addition, resveratrol abrogated the increased expression of HMGB 1-mediated signaling pathway, oxidative stress, fibrosis, and inflammation in diabetic hearts. In conclusion, inhibition of HMGB 1-mediated signaling pathway and oxidative stress may contribute to resveratrol-induced anti-inflammatory and antifibrotic effects in DCM.