Salvianolic Acid B (Sal B) ameliorates myocardial fibrosis in diabetic cardiomyopathy through deubiquitinating Smad7

Abstract

Background Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia Miltiorrhiza Bunge, is commonly used in Chinese Traditional Medicine for the treatment of cardiovascular diseases. Sal B has shown protecting effects against myocardial fibrosis induced by diabetic cardiomyopathy(DCM) in our previous experiment. This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM. Methods In this study, a variety of methods were utilized to investigate the effects of Sal B on improving myocardial fibrosis induced by DCM in vivo and in vitro. These methods included weight measurement, blood glucose analysis, echocardiography, HE staining, Masson's trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-associated 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 Sal B could significantly improve cardiac function, inhibit collagen deposition and phenotypic transformation, ameliorate myocardial fibrosis in DCM by up-regulating Smad7, thereby inhibiting TGF-β1 signaling pathway. Additionally, cell experiments demonstrated Sal B could significantly inhibit the proliferation, migration, phenotypic transformation and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose(HG). Sal B could significantly decrease the ubiquitization modifications of Smad7, stabilize the protein expression of Smad7, therefore increase the protein expression of Smad7 in the CFs , inhibit TGF-β1 signaling pathway, that maybe a potential mechanism of Sal B in mitigating myocardial fibrosis induced by DCM. Conclusion In summary, this study revealed that Salvianolic acid B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, blocking the TGF-β1 signaling pathway.