Abstract
Diabetic cardiomyopathy (DCM) is associated with a greater risk of mortality in patients with diabetes mellitus. Currently, no specific treatment has been suggested for DCM treatment. This study demonstrated that myricetin (M) attenuated DCM-associated cardiac injury in mice subjected to streptozotocin (SZT) and in neonatal rat cardiomyocytes (NRCM) challenged with high glucose. In vivo investigation demonstrated 6 months of M treatment (200 mg/kg/d) significantly alleviated cardiac hypertrophy, apoptosis, and interstitial fibrosis. Mechanically, M treatment significantly increased the activity of Nrf2/HO-1 pathway, strengthening antioxidative stress capacity evidenced by reversed activities of GPx and SOD, and decreased MDA production. M treatment also inhibited IκBα/NF-κB pathway, resulting in reduced secretion of inflammation cytokines including IL-1β, TNF-α, and IL-6. Besides, the TGFβ/Smad3 signaling was also blunted in DCM mice treated with M. These beneficial effects of M treatment protected cardiomyocytes from apoptosis as shown by decreased TUNEL-positive nucleus, c-caspase 3, and Bax. Similar effects of M treatment could be reproduced in NRCM treated with high glucose. Furthermore, through silencing Nrf2 in NRCM, we found that the regulation of IκBα/NFκB by M was independent on its function on Nrf2. Thus, we concluded that M possesses potential protective effects on DCM through inhibiting IκBα/NFκB and enhancing Nrf2/HO-1.
Highlights
Diabetic cardiomyopathy (DCM) is a major cardiac complication contributing to the increased morbidity and mortality of diabetic patients [1]
DCM is characterized by a series of structural and functional abnormities including left ventricular dysfunction, cardiomyocyte apoptosis, and interstitial fibrosis, all of which are not resulting from coronary heart diseases, congenital heart diseases, or hypertension [1, 2]
The body weight (BW) and heart weight (HW) of STZ group decreased compared with control group (CON) group (Table 2)
Summary
Diabetic cardiomyopathy (DCM) is a major cardiac complication contributing to the increased morbidity and mortality of diabetic patients [1]. Multiple mechanisms have been involved in the pathogenesis of DCM, including oxidative stress, inflammation, disordered calcium handling, mitochondrial dysfunction, impaired energy metabolism, and interstitial fibrosis [1, 3,4,5]. Reactive oxygen species (ROS) are responsible for cellular oxidative stress [4]. The synthesis and degradation of ROS are physiological and keep the dynamic balance dependent on cellular endogenous antioxidant factors [6]. Under the conditions of DCM, the antioxidant factors, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and Nrf, are decreased in cardiac tissue [6, 7].
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