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

Overview

Journal Front Pharmacol

Date 2019 Oct 17

PMID 31616303

Citations 9

Authors

Yiping Li

Xiaofen Ruan

Xiaowen Xu

Cha Li

Tingting Qiang

Hua Zhou

Junjie Gao

Xiaolong Wang

Affiliations

Soon will be listed here.

Abstract

Shengmai injection (SMI), a traditional Chinese herbal medicine extracted from Panax ginseng C.A. Mey., (Thunb.) Ker Gawl., and (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.

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References

Wang Z, Ren J . Current status and future direction of Chinese herbal medicine. Trends Pharmacol Sci. 2002; 23(8):347-8. DOI: 10.1016/s0165-6147(02)02051-5. View

Manna P, Achari A, Jain S . Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice. Arch Biochem Biophys. 2017; 615:22-34. DOI: 10.1016/j.abb.2017.01.002. View

Haynes P, Campbell K . Myocardial hypertrophy reduces transmural variation in mitochondrial function. Front Physiol. 2014; 5:178. PMC: 4019838. DOI: 10.3389/fphys.2014.00178. View

Zhan S, Fan X, Zhang F, Wang Y, Kang L, Li Z . A proteomic study of Shengmai injection's mechanism on preventing cardiac ischemia-reperfusion injury via energy metabolism modulation. Mol Biosyst. 2014; 11(2):540-8. DOI: 10.1039/c4mb00161c. View

Zhou Q, Qin W, Liu S, Kwong J, Zhou J, Chen J . Shengmai (a traditional Chinese herbal medicine) for heart failure. Cochrane Database Syst Rev. 2014; (4):CD005052. DOI: 10.1002/14651858.CD005052.pub5. View

Javadov S, Karmazyn M . Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection. Cell Physiol Biochem. 2007; 20(1-4):1-22. DOI: 10.1159/000103747. View

Javadov S, Rajapurohitam V, Kilic A, Zeidan A, Choi A, Karmazyn M . Anti-hypertrophic effect of NHE-1 inhibition involves GSK-3beta-dependent attenuation of mitochondrial dysfunction. J Mol Cell Cardiol. 2009; 46(6):998-1007. DOI: 10.1016/j.yjmcc.2008.12.023. View

Ghnenis A, Odhiambo J, McCormick R, Nathanielsz P, Ford S . Maternal obesity in the ewe increases cardiac ventricular expression of glucocorticoid receptors, proinflammatory cytokines and fibrosis in adult male offspring. PLoS One. 2017; 12(12):e0189977. PMC: 5739430. DOI: 10.1371/journal.pone.0189977. View

Chen Y, Wang Y, Chen J, Chen X, Cao W, Chen S . Roles of transcriptional corepressor RIP140 and coactivator PGC-1α in energy state of chronically infarcted rat hearts and mitochondrial function of cardiomyocytes. Mol Cell Endocrinol. 2012; 362(1-2):11-8. DOI: 10.1016/j.mce.2012.03.023. View

10.

Oakhill J, Steel R, Chen Z, Scott J, Ling N, Tam S . AMPK is a direct adenylate charge-regulated protein kinase. Science. 2011; 332(6036):1433-5. DOI: 10.1126/science.1200094. View

11.

Roman M, Ganau A, Saba P, Devereux R . Left ventricular hypertrophy, arterial compliance, and aging. Adv Exp Med Biol. 1997; 432:13-22. DOI: 10.1007/978-1-4615-5385-4_2. View

12.

Guo X, Jiang Q, Tuccitto A, Chan D, Alqawlaq S, Won G . The AMPK-PGC-1α signaling axis regulates the astrocyte glutathione system to protect against oxidative and metabolic injury. Neurobiol Dis. 2018; 113:59-69. DOI: 10.1016/j.nbd.2018.02.004. View

13.

Yamaguchi S, Katahira H, Ozawa S, Nakamichi Y, Tanaka T, Shimoyama T . Activators of AMP-activated protein kinase enhance GLUT4 translocation and its glucose transport activity in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab. 2005; 289(4):E643-9. DOI: 10.1152/ajpendo.00456.2004. View

14.

Guzun R, Timohhina N, Tepp K, Gonzalez-Granillo M, Shevchuk I, Chekulayev V . Systems bioenergetics of creatine kinase networks: physiological roles of creatine and phosphocreatine in regulation of cardiac cell function. Amino Acids. 2011; 40(5):1333-48. DOI: 10.1007/s00726-011-0854-x. View

15.

Karwi Q, Uddin G, Ho K, Lopaschuk G . Loss of Metabolic Flexibility in the Failing Heart. Front Cardiovasc Med. 2018; 5:68. PMC: 5997788. DOI: 10.3389/fcvm.2018.00068. View

16.

Wlodkowic D, Skommer J, Darzynkiewicz Z . Cytometry of apoptosis. Historical perspective and new advances. Exp Oncol. 2012; 34(3):255-62. PMC: 3476471. View

17.

Xian S, Yang Z, Lee J, Jiang Z, Ye X, Luo L . A randomized, double-blind, multicenter, placebo-controlled clinical study on the efficacy and safety of Shenmai injection in patients with chronic heart failure. J Ethnopharmacol. 2016; 186:136-142. DOI: 10.1016/j.jep.2016.03.066. View

18.

Scott G, Colligan P, Ren B, Ren J . Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide. Br J Pharmacol. 2001; 134(6):1159-65. PMC: 1573065. DOI: 10.1038/sj.bjp.0704377. View

19.

Chen Y, Tang Y, Zhang Y, Huang X, Xie Y, Xiang Y . A metabolomic study of rats with doxorubicin-induced cardiomyopathy and Shengmai injection treatment. PLoS One. 2015; 10(5):e0125209. PMC: 4418690. DOI: 10.1371/journal.pone.0125209. View

20.

Kulikova T, Stepanova O, Voronova A, Valikhov M, Sirotkin V, Zhirov I . Pathological Remodeling of the Myocardium in Chronic Heart Failure: Role of PGC-1α. Bull Exp Biol Med. 2018; 164(6):794-797. DOI: 10.1007/s10517-018-4082-1. View