Shengmai Injection Suppresses Angiotensin II-Induced Cardiomyocyte Hypertrophy and Apoptosis via Activation of the AMPK Signaling Pathway Through Energy-Dependent Mechanisms.

Yiping Li,Cha Li,Hua Zhou,Tingting Qiang,Xiaofen Ruan,Junjie Gao,Xiaowen Xu,Xiaolong Wang

doi:10.3389/fphar.2019.01095

Abstract

Shengmai injection (SMI), a traditional Chinese herbal medicine extracted from Panax ginseng C.A. Mey., Ophiopogon japonicus (Thunb.) Ker Gawl., and Schisandra chinensis (Turcz.) Baill., has been used to treat acute and chronic heart failure. This study aimed to further clarify the effects of SMI on energy metabolism. SMI could improve cell-survival rate and also reduce myocardial cell hypertrophy and apoptosis. Mitochondria are important sites of cellular energy metabolism, and SMI protects mitochondrial function which was evaluated by mitochondrial ultrastructure, mitochondrial respiratory control ratio (RCR), and mitochondrial membrane potential (ΔΨm) in this study. The expression levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and phosphocreatine (PCr) increased. The expression levels of free fatty acid oxidation [carnitine palmitoyltransferase-1 (CPT-1)], glucose oxidation [glucose transporter-4 (GLUT-4)], and mitochondrial biogenesis-related genes (peroxisome proliferator-activated receptor-γ coactivator-1α [PGC-1α]) were upregulated after SMI treatment. AMP-activated protein kinase (AMPK) is an important signaling pathway regulating energy metabolism and also can regulate the above-mentioned indicators. In the present study, SMI was found to promote phosphorylation of AMPK. However, the effects of SMI on fatty acid, glucose oxidation, mitochondrial biogenesis, as well as inhibiting apoptosis of hypertrophic cardiomyocytes were partly blocked by AMPK inhibitor–compound C. Moreover, decreased myocardial hypertrophy and apoptosis treated by SMI were inhibited by AMPK knockdown with shAMPK to a certain degree and AMPK knockdown almost abolished the SMI-induced increase in the expression of GLUT-4, CPT-1, and PGC-1α. These data suggest that SMI suppressed Ang II–induced cardiomyocyte hypertrophy and apoptosis via activation of the AMPK signaling pathway through energy-dependent mechanisms.

Highlights

Heart failure (HF) is a major public health concern, affecting more than 6.2 million people in the USA (Benjamin et al, 2019) and more than 23 million people worldwide (Go et al, 2013)
RT-qPCR was used to quantify the RNA levels of the hypertrophic markers, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC), in cardiomyocytes to determine the concentrations of Ang II and Shengmai injection (SMI)
Ang II (0.8 μM) caused the maximum increase in the mRNA expression of ANP, BNP, and β-MHC compared with the blank group (Figure 1A-a)

Summary

Introduction

Heart failure (HF) is a major public health concern, affecting more than 6.2 million people in the USA (Benjamin et al, 2019) and more than 23 million people worldwide (Go et al, 2013). The pathogenesis of HF is pathological cardiac remodeling, manifested as left ventricular dilatation, myocardial cell hypertrophy, and interstitial fibrosis (Opie et al, 2006; Shah et al, 2012). Cardiomyocyte hypertrophy is the main cause of decreased myocardial cell contractility and decreased blood supply capacity (Roman et al, 1997). The 1-year mortality rate of HF has only slightly declined, and its 5-year mortality rate has not declined during the last 10 years (Benjamin et al, 2019)

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