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Background <p>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.</p> Methods <p>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.</p> Results <p>SAL (0–320&#xa0;μM) treatment for 24&#xa0;h did not negatively impact CFs cell viability, and when the concentration was 40&#xa0;μM and above, SAL increased LDH release from MF cells. SAL (40–160&#xa0;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 (<i>P</i> &lt; 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 (<i>P</i> &lt; 0.05). In addition, SAL was also effective in ameliorating myocardial fibrosis in rats, whereas the SIRT1 inhibitor and EZH2 adenovirus attenuated the effect of SAL.</p> Conclusion <p>SAL ameliorates Ang II-induced fibrosis in CFs cells through modulation of the SIRT1/EZH2 pathway, which has therapeutic potential for myocardial fibrosis treatment.</p> Graphical abstract <p></p>

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Salidroside attenuates myocardial fibrosis through hindering oxidative stress and inflammation via SIRT1/EZH2 signaling pathway

  • 期刊论文

  • 发表日期：

    2026年1月20日

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  • Wenxue Jin,
  • Xiulan Qiao

摘要

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 inhibitor and EZH2 adenovirus attenuated the effect of SAL.

Conclusion

SAL ameliorates Ang II-induced fibrosis in CFs cells through modulation of the SIRT1/EZH2 pathway, which has therapeutic potential for myocardial fibrosis treatment.

Graphical abstract