Yixin-Shu Capsules Ameliorated Ischemia-Induced Heart Failure by Restoring Trx2 and Inhibiting JNK/p38 Activation.

Changpei Xiang,Jinhuan Gao,Hongjun Yang,Mao Zhang,Yi Zhang,Fangbo Zhang,Rui Zhou,Jingjing Zhang,Junying Wei,Feifei Guo,Ping Wang

doi:10.1155/2021/8049079

Abstract

Traditional Chinese medicine has shown great safety and efficacy in the treatment of heart failure (HF), whereas the mechanism remains unclear. In this study, the protective effect of Yixin-shu (YXS) capsules, a conventional medicine for various cardiovascular diseases, against myocardial ischemia-induced HF in rats was systematically investigated by RNA-seq technology. HF rats treated with YXS (0.8 or 1.6 g/kg/d, ig) for 6 weeks had significantly decreased brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and collagen III and attenuated cardiac structure rupture and collagen deposition. Additionally, YXS treatment decreased the levels of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and lactate dehydrogenase (LDH) and TUNEL-positive rate and the nitrotyrosine staining, but increased levels of glutathione (GSH), total antioxidant capacity (T-AOC) activity, and mitochondrial membrane potential. Further experiments demonstrated that YXS restored Trx2 and inhibited the phosphorylation of JNK and p38, thereby improving cardiac function in the rats with HF. Silencing Trx2 decreased the protection of YXS in the response to H2O2 as evidenced by the increase of caspase-3 activity and decrease of GSH level. Thus, YXS enhanced heart function and decreased myocardial damage through restoring Trx2 and inhibiting JNK and p38 activation in ischemia-induced HF.

Highlights

Heart failure (HF), characterized by reduced heart contractility and cardiac function, is an end stage of various cardiovascular diseases, which results in serious myocardial injury at the beginning and leads to damage of many other organs in the end [1]
The increase of collagen III in HF was reduced by YXS or VST treatment, and this was consistent with the Masson staining result, further confirming the attenuation of myocardial fibrosis by YXS and VST
An obvious reduction in left ventricular ejection fraction (Δ%LVEF) was found in the HF group, indicating an obvious myocardial dysfunction occurred in the HF group

Summary

Introduction

Heart failure (HF), characterized by reduced heart contractility and cardiac function, is an end stage of various cardiovascular diseases, which results in serious myocardial injury at the beginning and leads to damage of many other organs in the end [1]. Multiple insults including myocardial ischemia, atherosclerosis, hypertension, cardiomyopathy, and genetic problems cause myocardial damage and result in HF. Among all these insults, myocardial ischemia has emerged as one of the major causes of HF in recent decades. Myocardial ischemia has emerged as one of the major causes of HF in recent decades Several symptoms such as cardiomyocyte hypertrophy, elevated neurohumoral level, and enhanced filling pressure happened which attempted to compensate the dysfunction of the heart and resulted in the acceleration of cardiac remodeling and contraction declining [2, 3].

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Conclusion