Abstract
Andrographolide (Andro), a major bioactive component obtained from Andrographis paniculata Nees, has exerted wide antioxidant as well as cytoprotective properties. However, whether Andro treatment could retard the progress of diabetic cardiomyopathy (DCM) remains unknown. In this study, we evaluated the effects of Andro against diabetes-induced myocardial dysfunction and explored the underlying mechanism in STZ-induced diabetic mice. As a result, treatment with Andro dose dependently suppressed cardiac inflammation and oxidative stress, accompanied by decreasing cardiac apoptosis, which subsequently ameliorated cardiac fibrosis and cardiac hypertrophy. Further, Andro blocked hyperglycemia-triggered reactive oxygen species (ROS) generation by suppressing NADPH oxidase (NOX) activation and augmenting nuclear factor erythroid 2-related factor 2 (Nrf2) expression both in vitro and in vivo. Our results suggest that the cardioprotective effects afforded by Andro treatment involve the modulation of NOX/Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. The present study unravels the therapeutic potential of Andro in the treatment of DCM by attenuating oxidative stress, inflammation, and apoptosis.
Highlights
Diabetic cardiomyopathy (DCM) is characterized by myocardial left ventricular dysfunction, accompanied by the development of cardiac fibrosis, cardiac hypertrophy, and cardiomyocyte apoptosis [1]
Our work showed for the first time that Andro treatment dose dependently attenuated cardiac inflammation, oxidative damage, and cardiac apoptosis, which subsequently improved cardiac function in diabetic mice
We found the expression of NOX2, NOX4, and p47phox was elevated while the expression of the Nrf2directed heme oxygenase-1 (HO-1) expression was decreased, suggesting that NADPH oxidase (NOX)/nuclear factor erythroid 2related factor 2 (Nrf2) imbalance existed in both the diabetic myocardium and HG-stimulated H9c2 cardiomyoblasts
Summary
Diabetic cardiomyopathy (DCM) is characterized by myocardial left ventricular dysfunction, accompanied by the development of cardiac fibrosis, cardiac hypertrophy, and cardiomyocyte apoptosis [1]. Chronic hyperglycaemia contributes to myocardial injury and fibrosis, in the absence of underlying coronary artery disease and systemic hypertension, which subsequently induces heart failure [2, 3]. There are currently no effective approaches to protect against or halt DCM in the clinic. Intensive glycemic control can only slow down but not reverse the progression of heart failure [4]. DCM is still the leading cause of morbidity and mortality in diabetics.
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