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

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.

Energy metabolism disorders and potential therapeutic drugs in heart failure

“…extracts. It inhibits myocardial cell hypertrophy and apoptosis by activating the AMPK energy-dependent signaling pathway 195 . Shenfu granules are composed of Panax ginseng C.A.…”

Mitochondria-Endoplasmic Reticulum Contacts: The Promising Regulators in Diabetic Cardiomyopathy

“…Ker Gawl., and Schisandra chinensis (Turcz.) Baill., can activate the AMPK signaling pathway [ 103 ]. As AMPK regulates FUNDC1 expression, targeting AMPK may provide a cardioprotective effect.…”

A Quantitative Serum Proteomic Analysis Helps to Explore the Comprehensive Mechanism and Identify Serum Biomarkers of Shengmai Injection’s Effect on Isoproterenol-Induced Myocardial Ischemia in Rats

“…The biological pathway analysis helps reveal what biological reactions that drug intervention can trigger, and it is most important for guidance of therapeutic target discovery and treatment strategy suggestion. Some pharmacological studies reported SMI’s effects of anti-inflammatory, anti-oxidation, and suppression of cell apoptosis through pathways such as caspase-3, mTOR, JNK, AKT, ERK1/2, and AMPK ( Li et al, 2019 ; Zhu et al, 2019 ; Cao et al, 2020 ). Recently, Jiang et al ( Jiang et al, 2020 ) used systemic pharmacology and chemoinformatics to predict signaling pathways, biological processes, and targets of Shengmai Yin (including SMI) therapeutic role in coronary heart disease.…”

“…SMI prevented myocardial ischemia reperfusion injury by reducing myocardial apoptosis and enhancing vascular endothelial growth factor (VEGF)–related angiogenesis ( Lin et al, 2018 ). In addition, the related mechanism studies revealed SMI alleviated oxidative stress by activation of AKT and inhibition of ERK pathways ( Zhu et al, 2019 ) and suppressed cardiomyocyte hypertrophy via activation of the AMPK signaling pathway ( Li et al, 2019 ). However, all these studies focusing on SMI’s minority action targets and its comprehensive regulation mechanisms with the nature of multicomponent and multi-target are still poorly understood.…”