Abstract

Natural products with antioxidative activities are widely applied to prevent and treat various oxidative stress related diseases, including ischemic heart disease. However, the cellular and molecular mechanisms of those therapies are still needed to be illustrated. In this study, we characterized the cardioprotective effects of Hongjingtian Injection (HJT), an extensively used botanical drug for treating coronary heart disease. The H/R-induced profound elevation of oxidative stress was suppressed by HJT. HJT also attenuates oxidative injury by promoting cell viability, intracellular ATP contents, and mitochondrial oxygen consumption. Validation experiments indicated that HJT inhibited H/R-induced apoptosis and regulated the expression of apoptosis-associated proteins Bcl-2 and cleaved caspase3. Interestingly, HJT significantly regulated the expression of autophagy-related proteins LC3, Beclin, and mTOR as well as ERK and AKT. We provide evidence that the mechanism involves activation of AKT/Beclin-1, AKT, and ERK/mTOR pathway in cardiomyocyte autophagy. Histological and physiological evaluation revealed that HJT significantly decreased the infarct area of the heart, improved cardiac function, and increased the expression of LC3B in a rat model of coronary occlusion. From the obtained data, we proposed that HJT diminished myocardial oxidative damage through regulating the balance of autophagy and apoptosis and reducing oxidative stress.

Highlights

  • In the recent years, there has been a growing recognition of the importance of oxidative stress to pathogenic progress of various chronic diseases, as well as for the development of novel therapies [1]

  • We provide evidence that the mechanism involves activation of AKT/Beclin-1, AKT, and ERK/mTOR pathway in cardiomyocyte autophagy

  • We examined the cardioprotective effects of Hongjingtian Injection (HJT) against oxidative stress both in H/R-induced myocardial injured cells and in myocardial ischemia-injured rats and hypothesized that the protection mechanism of HJT might be associated with the enhancement of the antioxidant system

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Summary

Introduction

There has been a growing recognition of the importance of oxidative stress to pathogenic progress of various chronic diseases, as well as for the development of novel therapies [1]. Recent biological and pharmacological investigations showed that HJT can dilate the coronary artery and reduce cardiac afterload in dog [6]. The extracts of Rhodiola rosea L., another medicinal plant in Eastern Europe which contains similar chemical constituents of HJT, are regarded to stimulate the nervous system; enhance physical and mental performance; and treat fatigue, psychological stress, and depression [7]. Recent reports showed that salidroside, an active ingredient of the root of Rhodiola rosea L., possessed a range of Oxidative Medicine and Cellular Longevity pharmacological properties, including antihypoxia, antiinflammation, antioxidative, anticancer, antiaging, and neuroprotective effects [8,9,10,11,12], especially the therapeutic action of salidroside in cardioprotective effects which has been well documented in the laboratory [13]. HJT exerts a large variety of biological activities, such as promoting the activities of antioxidant enzymes [14], increasing tolerance to hypoxia [11], an unclear pharmacological mechanism of action, has become a common problem faced in clinical application

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