Cardioprotective effects of polydatin against myocardial injury in diabetic rats via inhibition of NADPH oxidase and NF-κB activities

Abstract

Background Diabetic cardiomyopathy is a main cause of the increased morbidity in diabetic patients, no effective treatment is available so far. Polydatin, a resveratrol glucoside isolated from the Polygonum cuspidatum, was found by our and others have antioxidant and cardioprotective activities. Therapeutic effects of polydatin on diabetic cardiomyopathy and the possible mechanisms remains unclear. This study aimed to investigate the cardioprotective effects and underlying mechanisms of polydatin on myocardial injury induced by hyperglycemia. Methods Diabetes in rats was made by high-fat diet combined with multiple low doses of streptozotocin, and then treated with polydatin (100 mg·kg-1·day-1, by gavage) for 8 weeks. Cardiac function was examined by echocardiography. Myocardial tissue and blood samples were collected for histology, protein and metabolic characteristics analysis. In cultured H9c2 cells with 30 mM of glucose, the direct effects of polydatin on myocyte injury were also observed. Results In diabetic rats, polydatin administration significantly improved myocardial dysfunction and attenuated histological abnormalities, as evidenced by elevating left ventricular shortening fraction and ejection fraction, as well as reducing cardiac hypertrophy and interstitial fibrosis. In cultured H9c2 cells, pretreatment of polydatin dose-dependently inhibited high glucose-induced cardiomyocyte injury. Further observation evidenced that polydatin suppressed the increase in the reactive oxygen species levels, NADPH oxidase activity and inflammatory cytokines production induced by hyperglycemia in vivo and in vitro. Polydatin also prevented the increase expression of NOX4, NOX2 and NF-κB in the high glucose -stimulated H9c2 cells and diabetic hearts. Conclusions Our results demonstrate that the cardioprotective effect of polydatin against hyperglycemia-induced myocardial injury is mediated by inhibition of NADPH oxidase and NF-κB activity. The findings may provide a novel understanding the mechanisms of the polydatin to be a potential treatment of diabetic cardiomyopathy.

Effects of Naringin on Cardiomyocytes From a Rodent Model of Type 2 Diabetes

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Polydatin Protects Against Articular Cartilage Degeneration by Regulating Autophagy Mediated by AMPK/Mtor Signaling Pathway

“…mTOR could improve the autophagy activity and reduce the apoptosis of chondrocytes in a KOA, further reduce the degree of OA [28]. It has been proved that polydatin regulated important molecules involved in autophagy and in ammation signaling pathways in bovine mammary epithelial cells [29], acute kidney injury [30,31] and myocardial injury in diabetic rats [32,33]. In this study, it was found that the effects of polydatin on autophagy induction was mTORdependent and regulated by AMPK.…”

Polydatin Reduces Cardiotoxicity and Enhances the Anticancer Effects of Sunitinib by Decreasing Pro-Oxidative Stress, Pro-Inflammatory Cytokines, and NLRP3 Inflammasome Expression

“…A recent study demonstrated that polydatin reduces tissue damages induced by hyperglycemia and hyperlipidemia, increasing cardiovascular functions during diabetes (86,87). In another preclinical trial, 8-weeks polydatin treatment significantly improved the diastolic and systolic dysfunction, attenuated hypertrophy and interstitial fibrosis in mice with diabetes (88). Other similar studies suggested that polydatin protects cardiomyocytes heart failure also in non-diabetic models through reduction of iROS, pro-inflammatory prostaglandins and cytokines (89, 90).…”