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Extract of Sheng-Mai-San ameliorates myocardial Ischemia-Induced heart failure by modulating ca2+-Calcineurin-Mediated DRP1 signaling pathways
Yang Y.2; Tian Y.2; Hu S.2; Bi S.2; Li S.2; Hu Y.1; Kou J.2; Qi J.2; Yu B.2
2017-09-01
Source PublicationInternational Journal of Molecular Sciences
ISSN14220067 16616596
Volume18Issue:9
AbstractSheng-Mai-San (SMS) is a well-known traditional Chinese medicine (TCM) complex prescription used to treat heart failure (HF) and angina in clinic. However, its potential therapeutic mechanisms remain unclear. The present study evaluated the cardioprotection of extract of SMS (ESMS) on myocardial ischemia (MI)-induced HF, and explored the underlying molecular mechanisms. The results demonstrated that ESMS (728.0 mg/kg) significantly attenuated MI injury-induced HF by improving cardiac function and pathological changes, decreasing lactate dehydrogenase (LDH), creatine kinase (CK) activities, and brain natriuretic peptide (BNP) levels, increasing ATPase activity, and reducing intracellular Ca levels in MI-induced HF mice model. It also significantly decreased the apoptotic index. In vitro, ESMS (400 μg/mL) inhibited mitochondrial-dependent myocardial apoptosis by modulating the expression of caspase-3 and the Bcl-2/Bax ratio, and improved mitochondrial function through increasing mitochondrial membrane potential and cellular ATP content. ESMS restored intracellular Ca and downregulated the expression of Calcineurin A (CnA), thus inhibiting phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and increasing phosphorylation of Drp1 at Ser637 to prevent cardiomyocyte mitochondrial fission. Above-mentioned results demonstrated ESMS suppressed mitochondrial-mediated apoptosis in oxygen glucose deprivation (OGD) injured H9c2 cardiomyocytes. These findings suggested that ESMS attenuated MI-induced HF by regulating Ca homeostasis and suppressing mitochondrial mediated apoptosis through the modulation of Ca-calcineurin-mediated Drp1 signaling pathways. Our results provide insight into the mechanism and clinical applications of SMS and suggest a potential therapeutic strategy for HF.
KeywordCalcineurin A Dynamin-related protein 1 Extract of Sheng-Mai-San Heart failure Mitochondrial fission
DOI10.3390/ijms18091825
URLView the original
Language英語
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Universidade de Macau
2.China Pharmaceutical University
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GB/T 7714
Yang Y.,Tian Y.,Hu S.,et al. Extract of Sheng-Mai-San ameliorates myocardial Ischemia-Induced heart failure by modulating ca2+-Calcineurin-Mediated DRP1 signaling pathways[J]. International Journal of Molecular Sciences,2017,18(9).
APA Yang Y..,Tian Y..,Hu S..,Bi S..,Li S..,...&Yu B..(2017).Extract of Sheng-Mai-San ameliorates myocardial Ischemia-Induced heart failure by modulating ca2+-Calcineurin-Mediated DRP1 signaling pathways.International Journal of Molecular Sciences,18(9).
MLA Yang Y.,et al."Extract of Sheng-Mai-San ameliorates myocardial Ischemia-Induced heart failure by modulating ca2+-Calcineurin-Mediated DRP1 signaling pathways".International Journal of Molecular Sciences 18.9(2017).
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