Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries

Abstract Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of...

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Autores principales:	Yu-Hui Sun, Ren Bu, Yue-Wu Wang, Yu-Chong Hu, Xu-Mei Wang, Xin Dong, Wen Zu, Yan Niu, Peng-Wei Zhao, Peng Sun, Shi-Hang Ru, Jing-Kun Lu, Sheng-Sang Na
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/658866cb539b473ca894f724d1e8f20c
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spelling	oai:doaj.org-article:658866cb539b473ca894f724d1e8f20c2021-12-02T14:12:45ZValidation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries10.1038/s41598-020-80861-62045-2322https://doaj.org/article/658866cb539b473ca894f724d1e8f20c2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80861-6https://doaj.org/toc/2045-2322Abstract Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H2O2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H2O2-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX’s cardioprotection effect.Yu-Hui SunRen BuYue-Wu WangYu-Chong HuXu-Mei WangXin DongWen ZuYan NiuPeng-Wei ZhaoPeng SunShi-Hang RuJing-Kun LuSheng-Sang NaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yu-Hui Sun Ren Bu Yue-Wu Wang Yu-Chong Hu Xu-Mei Wang Xin Dong Wen Zu Yan Niu Peng-Wei Zhao Peng Sun Shi-Hang Ru Jing-Kun Lu Sheng-Sang Na Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries
description	Abstract Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H2O2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H2O2-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX’s cardioprotection effect.
format	article
author	Yu-Hui Sun Ren Bu Yue-Wu Wang Yu-Chong Hu Xu-Mei Wang Xin Dong Wen Zu Yan Niu Peng-Wei Zhao Peng Sun Shi-Hang Ru Jing-Kun Lu Sheng-Sang Na
author_facet	Yu-Hui Sun Ren Bu Yue-Wu Wang Yu-Chong Hu Xu-Mei Wang Xin Dong Wen Zu Yan Niu Peng-Wei Zhao Peng Sun Shi-Hang Ru Jing-Kun Lu Sheng-Sang Na
author_sort	Yu-Hui Sun
title	Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries
title_short	Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries
title_full	Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries
title_fullStr	Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries
title_full_unstemmed	Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries
title_sort	validation of efficacy and mechanism of sanwei-tanxiang powder in improving myocardial ischemia reperfusion injuries
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/658866cb539b473ca894f724d1e8f20c
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Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries

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