Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

Abstract Background Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia miltiorrhiza Bunge, is commonly used in Traditional Chinese Medicine to treat cardiovascular disease. In our previous study, Sal B protected against myocardial fibrosis induced by diabetic cardiomyo...

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Main Authors: Hong Luo, Lingyun Fu, Xueting Wang, Yini Xu, Ling Tao, Xiangchun Shen
Format: Article
Language:English
Published: BMC 2023-12-01
Series:Chinese Medicine
Subjects:
Online Access:https://doi.org/10.1186/s13020-023-00868-9
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author Hong Luo
Lingyun Fu
Xueting Wang
Yini Xu
Ling Tao
Xiangchun Shen
author_facet Hong Luo
Lingyun Fu
Xueting Wang
Yini Xu
Ling Tao
Xiangchun Shen
author_sort Hong Luo
collection DOAJ
description Abstract Background Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia miltiorrhiza Bunge, is commonly used in Traditional Chinese Medicine to treat cardiovascular disease. In our previous study, Sal B protected against myocardial fibrosis induced by diabetic cardiomyopathy (DCM). This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM. Methods Various methods were used to investigate the effects of Sal B on myocardial fibrosis induced by DCM in vivo and in vitro. These methods included blood glucose measurement, echocardiography, HE staining, Masson’s trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-related protein expression (Collagen-I, Collagen-III, TGF-β1, p-Smad3, Smad3, Smad7, and α-smooth muscle actin), analysis of Smad7 gene expression, and analysis of Smad7 ubiquitin modification. Results The animal test results indicated that Sal B significantly improved cardiac function, inhibited collagen deposition and phenotypic transformation, and ameliorated myocardial fibrosis in DCM by upregulating Smad7, thereby inhibiting the TGF-β1 signaling pathway. In addition, cell experiments demonstrated that Sal B significantly inhibited the proliferation, migration, phenotypic transformation, and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose (HG). Sal B significantly decreased the ubiquitination of Smad7 and stabilized the protein expression of Smad7, thereby increasing the protein expression of Smad7 in CFs and inhibiting the TGF-β1 signaling pathway, which may be the potential mechanism by which Sal B mitigates myocardial fibrosis induced by DCM. Conclusion This study revealed that Sal B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, and blocking the TGF-β1 signaling pathway.
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spelling doaj.art-723c69442c394e098fa252d61351ed472023-12-17T12:29:55ZengBMCChinese Medicine1749-85462023-12-0118111310.1186/s13020-023-00868-9Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7Hong Luo0Lingyun Fu1Xueting Wang2Yini Xu3Ling Tao4Xiangchun Shen5The State Key Laboratory of Functions and Applications of Medicinal Plants, School of Basic Medical Sciences, Guizhou Medical UniversityThe Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical UniversityThe Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical UniversityThe State Key Laboratory of Functions and Applications of Medicinal Plants, School of Basic Medical Sciences, Guizhou Medical UniversityThe Experimental Animal Center of Guizhou Medical University, Guizhou Medical UniversityThe State Key Laboratory of Functions and Applications of Medicinal Plants, School of Basic Medical Sciences, Guizhou Medical UniversityAbstract Background Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia miltiorrhiza Bunge, is commonly used in Traditional Chinese Medicine to treat cardiovascular disease. In our previous study, Sal B protected against myocardial fibrosis induced by diabetic cardiomyopathy (DCM). This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM. Methods Various methods were used to investigate the effects of Sal B on myocardial fibrosis induced by DCM in vivo and in vitro. These methods included blood glucose measurement, echocardiography, HE staining, Masson’s trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-related protein expression (Collagen-I, Collagen-III, TGF-β1, p-Smad3, Smad3, Smad7, and α-smooth muscle actin), analysis of Smad7 gene expression, and analysis of Smad7 ubiquitin modification. Results The animal test results indicated that Sal B significantly improved cardiac function, inhibited collagen deposition and phenotypic transformation, and ameliorated myocardial fibrosis in DCM by upregulating Smad7, thereby inhibiting the TGF-β1 signaling pathway. In addition, cell experiments demonstrated that Sal B significantly inhibited the proliferation, migration, phenotypic transformation, and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose (HG). Sal B significantly decreased the ubiquitination of Smad7 and stabilized the protein expression of Smad7, thereby increasing the protein expression of Smad7 in CFs and inhibiting the TGF-β1 signaling pathway, which may be the potential mechanism by which Sal B mitigates myocardial fibrosis induced by DCM. Conclusion This study revealed that Sal B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, and blocking the TGF-β1 signaling pathway.https://doi.org/10.1186/s13020-023-00868-9Salvianolic acid BDiabetic cardiomyopathyMyocardial fibrosisTGF-β1 signaling pathwayDeubiquitinating Smad7
spellingShingle Hong Luo
Lingyun Fu
Xueting Wang
Yini Xu
Ling Tao
Xiangchun Shen
Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7
Chinese Medicine
Salvianolic acid B
Diabetic cardiomyopathy
Myocardial fibrosis
TGF-β1 signaling pathway
Deubiquitinating Smad7
title Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7
title_full Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7
title_fullStr Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7
title_full_unstemmed Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7
title_short Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7
title_sort salvianolic acid b ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating smad7
topic Salvianolic acid B
Diabetic cardiomyopathy
Myocardial fibrosis
TGF-β1 signaling pathway
Deubiquitinating Smad7
url https://doi.org/10.1186/s13020-023-00868-9
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