Shensongyangxin protects against pressure overload‑induced cardiac hypertrophy

Shen,Di‑Fei; Wu,Qing‑Qing; Ni,Jian; Deng,Wei; Wei,Cong; Jia,Zhen‑Hua; Zhou,Heng; Zhou,Meng‑Qiao; Bian,Zhou‑Yan; Tang,Qi‑Zhu

doi:10.3892/mmr.2015.4598

Shensongyangxin protects against pressure overload‑induced cardiac hypertrophy

Authors:
- Di‑Fei Shen
- Qing‑Qing Wu
- Jian Ni
- Wei Deng
- Cong Wei
- Zhen‑Hua Jia
- Heng Zhou
- Meng‑Qiao Zhou
- Zhou‑Yan Bian
- Qi‑Zhu Tang
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Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, The Integration of Traditional and Western Medical Research Academy of Hebei, Shijiazhuang, Hebei 050035, P.R. China
Published online on: November 23, 2015 https://doi.org/10.3892/mmr.2015.4598
Pages: 980-988

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Abstract

Shensongyangxin (SSYX) is a medicinal herb, which has long been used in traditional Chinese medicine. Various pharmacological activities of SSYX have been identified. However, the role of SSYX in cardiac hypertrophy remains to be fully elucidated. In present study, aortic banding (AB) was performed to induce cardiac hypertrophy in mice. SSYX (520 mg/kg) was administered by daily gavage between 1 and 8 weeks following surgery. The extent of cardiac hypertrophy was then evaluated by pathological and molecular analyses of heart tissue samples. In addition, in vitro experiments were performed to confirm the in vivo results. The data of the present study demonstrated that SSYX prevented the cardiac hypertrophy and fibrosis induced by AB, as assessed by measurements of heart weight and gross heart size, hematoxylin and eosin staining, cross‑sectional cardiomyocyte area and the mRNA expression levels of hypertrophic markers. SSYX also inhibited collagen deposition and suppressed the expression of transforming growth factor β (TGFβ), connective tissue growth factor, fibronectin, collagen Ⅰα and collagen Ⅲα, which was mediated by the inhibition of the TGFβ/small mothers against decapentaplegic (Smad) signaling pathway. The inhibitory action of SSYX on cardiac hypertrophy was mediated by the inhibition of Akt signaling. In vitro investigations in the rat H9c2 cardiac cells also demonstrated that SSYX attenuated angiotensin II‑induced cardiomyocyte hypertrophy. These findings suggested that SSYX attenuated cardiac hypertrophy and fibrosis in the pressure overloaded mouse heart. Therefore, the cardioprotective effect of SSYX is associated with inhibition of the Akt and TGFβ/Smad signaling pathways.

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1	Rosca MG, Tandler B and Hoppel CL: Mitochondria in cardiac hypertrophy and heart failure. J Mol Cell Cardiol. 55:31–41. 2013. View Article : Google Scholar :
2	Foryst-Ludwig A and Kintscher U: Sex differences in exercise-induced cardiac hypertrophy. Pflugers Arch. 465:731–737. 2013. View Article : Google Scholar : PubMed/NCBI
3	Abel ED and Doenst T: Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovasc Res. 90:234–242. 2011. View Article : Google Scholar : PubMed/NCBI
4	Hou J and Kang Y: Regression of Pathological Cardiac Hypertrophy: Signaling pathways and therapeutic targets. Pharmacol Ther. 135:337–354. 2012. View Article : Google Scholar : PubMed/NCBI
5	Pillai VB, Sundaresan N and Gupta MP: Regulation of Akt signaling by sirtuins: Its implication in cardiac hypertrophy and aging. Circ Res. 114:368–378. 2014. View Article : Google Scholar : PubMed/NCBI
6	Creemers EE and Pinto Y: Molecular mechanisms that control interstitial fibrosis in the pressure-overloaded heart. Cardiovasc Res. 89:265–272. 2011. View Article : Google Scholar
7	Oka T, Akazawa H, Naito AT and Komuro I: Angiogenesis and cardiac hypertrophy: Maintenance of cardiac function and causative roles in heart failure. Circ Res. 114:565–571. 2014. View Article : Google Scholar : PubMed/NCBI
8	Liu ZHJ, Hu R, Huo Y, Gong J, Zhang Y, Wei C and Pu J: Gene expression profile of increased heart rate in shensongyangxin-treated bradycardia rabbits. Evid Based Complement Alternat Med. 2014:7159372014. View Article : Google Scholar : PubMed/NCBI
9	Liu Y, Li N, Jia Z, Lu F and Pu J: Chinese medicine shensongyangxin is effective for patients with bradycardia: Results of a randomized, double-blind, placebo-controlled multicenter trial. Evid Based Complement Alternat Med. 2014:6057142014. View Article : Google Scholar : PubMed/NCBI
10	Wang AH, Pu JL, Qi XY, Miao WL, Hou ZS, Cong HL, Zhou JZ, Liu XF, Li SM and Han QH: Evaluation of shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation: A randomized, double-blind and controlled multicenter trial. Zhonghua Yi Xue Za Zhi. 91:1677–1681. 2011.In Chinese. PubMed/NCBI
11	Zou JG, Zhang J, Jia ZH and Cao KJ: Evaluation of the traditional Chinese Medicine Shensongyangxin capsule on treating premature ventricular contractions: A randomized, double-blind, controlled multicenter trial. Chin Med J (Engl). 124:76–83. 2011.
12	Yang Z, Yu X and Yu ML: Effects of shensongyangxin capsule on heart rate turbulence and heart rate variability in chronic heart failure. Chin Med J (Engl). 126:4389–4391. 2013.
13	Chai S, Wang S, Yao L, Wu A, Liu Y and Rao C: Effect of shensongyangxin capsule on myocardial remodeling and ventricular fibrillation threshold value in rat with coronary artery ligation. Zhongguo Zhong Yao Za Zhi. 34:2101–2104. 2009.In Chinese. PubMed/NCBI
14	Yuan Y, Zong J, Zhou H, Bian ZY, Deng W, Dai J, Gan HW, Yang Z, Li H and Tang QZ: Puerarin attenuates pressure overload-induced cardiac hypertrophy. J Cardiol. 63:73–81. 2014. View Article : Google Scholar
15	Yan L, Wei X, Tang QZ, Feng J, Zhang Y, Liu C, Bian ZY, Zhang LF, Chen M, Bai X, et al: Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling. Cardiovasc Res. 92:85–94. 2011. View Article : Google Scholar : PubMed/NCBI
16	Aoyagi T and Matsui T: Phosphoinositide-3 kinase signaling in cardiac hypertrophy and heart failure. Curr Pharm Des. 17:1818–1824. 2011. View Article : Google Scholar : PubMed/NCBI
17	Skurk C, Izymiya Y, Maatz H, Razeghi P, Shiojima I, Sandri M, Sato K, Zeng L, Schiekofer S, Pimentel D, et al: The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling. J Biol Chem. 280:20814–20823. 2005. View Article : Google Scholar : PubMed/NCBI
18	Yu W, Chen C, Fu Y, Wang X and Wang W: Insulin signaling: A possible pathogenesis of cardiac hypertrophy. Cardiovasc Ther. 28:101–105. 2010. View Article : Google Scholar : PubMed/NCBI
19	Wu QQ, Zonj J, Gao L, Dai J, Yang Z, Xu M, Fang Y, Ma ZG and Tang QZ: Sulforaphane protects H9c2 cardiomyocytes from angiotensin II-induced hypertrophy. Herz. 39:390–396. 2014. View Article : Google Scholar
20	Maillet M, van Berlo JH and Molkentin JD: Molecular basis of physiological heart growth: Fundamental concepts and new players. Nat Rev Mol Cell Biol. 14:38–48. 2013. View Article : Google Scholar
21	Ni YG, Berenji K, Wang N, Oh M, Sachan N, Dey A, Cheng J, Lu G, Morris DJ, Castrillon DH, et al: FOXo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling. Circulation. 114:1159–1168. 2006. View Article : Google Scholar : PubMed/NCBI
22	Edgley AJ, Krum H and Kelly DJ: Targeting fibrosis for the treatment of heart failure: A role for transforming growth factor-β. Cardiovasc Ther. 30:e30–40. 2014. View Article : Google Scholar
23	Kamato D, Burch M, Piva TJ, Rezaei HB, Rostam MA, Xu S, Zheng W, Little PJ and Osman N: Transforming growth factor-β signalling: Role and consequences of Smad linker region phosphorylation. Cell Signal. 25:2017–2024. 2013. View Article : Google Scholar : PubMed/NCBI
24	Szabó Z, Magga J, Alakoski T, Ulvila J, Piuhola J, Vainio L, Kivirikko KI, Vuolteenaho O, Ruskoaho H, Lipson KE, et al: Connective tissue growth factor inhibition attenuates left ventricular remodeling and dysfunction in pressure overload-induced heart failure. Hypertension. 63:1235–1240. 2014. View Article : Google Scholar : PubMed/NCBI