Abstract

Background Salidroside (SAL) exhibits various pharmacological activities such as anti-inflammatory and anti-cancer. Sirtuin 1 (SIRT1)/Enhancer of Zeste Homolog 2 (EZH2) signaling pathway plays a key role in fibroblast proliferation and fibrosis. This study aims to elucidate whether SAL could ameliorate angiotensin II (Ang II)-mediated myocardial fibrosis through the SIRT1/EZH2 signaling pathway. Methods Primary cardiac fibroblasts (CFs) were obtained from the atria of SD rats, and CFs were induced using Ang II to transform into myofibroblasts (MFs), and both were characterized by immunofluorescence. CCK-8 assay assessed the impact of SAL on CFs cell viability, and LDH kit detected LDH release from MF cells. CFs cell biological behavior was assessed by EdU staining, Scratch-wound, and Transwell assay. ELISA kits measured SOD, CAT, MDA, and inflammatory factors levels, and RT-qPCR detected inflammatory factors expression. A myocardial fibrosis rat model was constructed, with the lesions were evaluated by pathological staining. In addition, Western blot detected fibrosis and SIRT1/EZH2 signaling pathway-related protein levels. Results SAL (0–320 μM) treatment for 24 h did not negatively impact CFs cell viability, and when the concentration was 40 μM and above, SAL increased LDH release from MF cells. SAL (40–160 μM) significantly inhibited aberrant proliferation of CFs cells caused by Ang II, and reduced migrating and invading cells number, improved fibrosis, and could increase SOD and CAT activities while decreasing MDA, ROS, and inflammatory factors levels ( P  < 0.05). Not only that, SAL increased SIRT1 level in CF cells while decreasing the EZH2 level. Knockdown SIRT1 or overexpression EZH2 significantly reduced the protective effect of SAL on CF cells ( P  < 0.05). In addition, SAL was also effective in ameliorating myocardial fibrosis in rats, whereas the SIRT1 inh