ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress

Yanting Lu, Shu Zhu, Xiaoyan Wang, Juhai Liu, Yingying Li, Wei Wang, Shijun Wang, Furong Wang College of TCM, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of ChinaCorrespondence: Shijun Wang; Furong Wang Email wsj@sdutcm.edu.cn; 15168888786@163.comB...

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Autores principales:	Lu Y, Zhu S, Wang X, Liu J, Li Y, Wang W, Wang S, Wang F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	diabetes myocardium shengmai-san oxidative stress ampk nox Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/2ef1402b9c6e4281856c10bbb55561eb
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spelling	oai:doaj.org-article:2ef1402b9c6e4281856c10bbb55561eb2021-12-02T12:14:54ZShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress1178-7007https://doaj.org/article/2ef1402b9c6e4281856c10bbb55561eb2021-02-01T00:00:00Zhttps://www.dovepress.com/shengmai-san-attenuates-cardiac-remodeling-in-diabetic-rats-by-inhibit-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Yanting Lu, Shu Zhu, Xiaoyan Wang, Juhai Liu, Yingying Li, Wei Wang, Shijun Wang, Furong Wang College of TCM, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of ChinaCorrespondence: Shijun Wang; Furong Wang Email wsj@sdutcm.edu.cn; 15168888786@163.comBackground and Purpose: ShengMai-San (SMS) is traditionally used to treat ischemic cardiovascular and cerebrovascular diseases. Recently, several studies have reported the cardioprotective effects of SMS in diabetic animals. However, the potential mechanisms have not yet been fully elucidated. In this study, we investigated whether SMS exerts a beneficial effect in diabetic cardiomyopathy (DCM) by alleviating NADPH oxidase (NOX)-mediated oxidative stress.Methods: SD rats were randomly divided into a negative control group (NC), diabetes mellitus group (DM) and SMS-treated group (SMS). The myocardial structure alterations, apoptosis and biomarkers of oxidative stress were observed. Moreover, to explore the protective mechanism of SMS, the activation of AMPKα, expression and translocation of NOX-related proteins were assessed.Results: Diabetes led to excessive collagen content, fibrosis, and apoptosis in the myocardium. Oxidative stress in diabetic hearts was indicated by low levels of T-AOC, high levels of 8-iso-PGF2α and 8-OHdG, inactivation of AMPKα, elevated expression of NOX2 and NOX4 and translocation of NOX isoforms p47phox and p67phox. Treatment with SMS for 10 weeks resulted in the alleviation of diabetes-associated myocardial structure abnormalities and apoptosis. Additionally, SMS attenuated the accumulation of oxidative stress markers in myocardial tissue. Further investigation showed that SMS was able to reverse the levels of oxidative stress-associated proteins NOX2 and NOX4 in the DM rats. Moreover, SMS treatment blunted the translocation of NADPH oxidase isoforms p47phox and p67phox as well. Furthermore, SMS promoted the activation of AMPK in the cardiac tissue of diabetic rats.Conclusion: These findings indicate that SMS exhibits therapeutic properties against diabetic cardiomyopathy by attenuating myocardial oxidative damage via activation of AMPKα and inhibition of NOX signaling.Keywords: diabetes, myocardium, ShengMai-San, oxidative stress, AMPK, NOXLu YZhu SWang XLiu JLi YWang WWang SWang FDove Medical Pressarticlediabetesmyocardiumshengmai-sanoxidative stressampknoxSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 647-657 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetes myocardium shengmai-san oxidative stress ampk nox Specialties of internal medicine RC581-951
spellingShingle	diabetes myocardium shengmai-san oxidative stress ampk nox Specialties of internal medicine RC581-951 Lu Y Zhu S Wang X Liu J Li Y Wang W Wang S Wang F ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress
description	Yanting Lu, Shu Zhu, Xiaoyan Wang, Juhai Liu, Yingying Li, Wei Wang, Shijun Wang, Furong Wang College of TCM, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of ChinaCorrespondence: Shijun Wang; Furong Wang Email wsj@sdutcm.edu.cn; 15168888786@163.comBackground and Purpose: ShengMai-San (SMS) is traditionally used to treat ischemic cardiovascular and cerebrovascular diseases. Recently, several studies have reported the cardioprotective effects of SMS in diabetic animals. However, the potential mechanisms have not yet been fully elucidated. In this study, we investigated whether SMS exerts a beneficial effect in diabetic cardiomyopathy (DCM) by alleviating NADPH oxidase (NOX)-mediated oxidative stress.Methods: SD rats were randomly divided into a negative control group (NC), diabetes mellitus group (DM) and SMS-treated group (SMS). The myocardial structure alterations, apoptosis and biomarkers of oxidative stress were observed. Moreover, to explore the protective mechanism of SMS, the activation of AMPKα, expression and translocation of NOX-related proteins were assessed.Results: Diabetes led to excessive collagen content, fibrosis, and apoptosis in the myocardium. Oxidative stress in diabetic hearts was indicated by low levels of T-AOC, high levels of 8-iso-PGF2α and 8-OHdG, inactivation of AMPKα, elevated expression of NOX2 and NOX4 and translocation of NOX isoforms p47phox and p67phox. Treatment with SMS for 10 weeks resulted in the alleviation of diabetes-associated myocardial structure abnormalities and apoptosis. Additionally, SMS attenuated the accumulation of oxidative stress markers in myocardial tissue. Further investigation showed that SMS was able to reverse the levels of oxidative stress-associated proteins NOX2 and NOX4 in the DM rats. Moreover, SMS treatment blunted the translocation of NADPH oxidase isoforms p47phox and p67phox as well. Furthermore, SMS promoted the activation of AMPK in the cardiac tissue of diabetic rats.Conclusion: These findings indicate that SMS exhibits therapeutic properties against diabetic cardiomyopathy by attenuating myocardial oxidative damage via activation of AMPKα and inhibition of NOX signaling.Keywords: diabetes, myocardium, ShengMai-San, oxidative stress, AMPK, NOX
format	article
author	Lu Y Zhu S Wang X Liu J Li Y Wang W Wang S Wang F
author_facet	Lu Y Zhu S Wang X Liu J Li Y Wang W Wang S Wang F
author_sort	Lu Y
title	ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress
title_short	ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress
title_full	ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress
title_fullStr	ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress
title_full_unstemmed	ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress
title_sort	shengmai-san attenuates cardiac remodeling in diabetic rats by inhibiting nox-mediated oxidative stress
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/2ef1402b9c6e4281856c10bbb55561eb
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ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress

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