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

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.