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Background <p>Myocardial infarction (MI) triggers adverse cardiac remodeling and fibrosis, leading to heart dysfunction. Myricetin, a natural flavonoid, has potential cardioprotective effects, but its mechanisms remain unclear. This study investigated whether myricetin alleviates MI-induced cardiac injury and fibrosis via SIRT1-mediated modulation of TGF-β1/Smad2/3 signaling.</p> Methods <p>A mouse MI model was established via left anterior descending (LAD) coronary artery ligation. Myricetin (100&#xa0;mg/kg/day, oral gavage) was administered for 7&#xa0;days pre-surgery, with the SIRT1 inhibitor EX527 (5&#xa0;mg/kg, intraperitoneal) co-administered in subsets. Primary cardiac fibroblasts were pretreated with myricetin (5–30&#xa0;μM) or SIRT1-targeted shRNA prior to angiotensin II (Ang II, 100&#xa0;nM) exposure. Fibrosis, protein/mRNA expression, and cardiac function were assessed using histological (Masson's trichrome, TTC staining), molecular (Western blot, qPCR, immunofluorescence), and functional (echocardiography, transwell migration) analyses.</p> Results <p>Myricetin reduced infarct size (p &lt; 0.01), improved cardiac function (decreased LVIDd/LVIDs, increased LVEF/LVFS) (p &lt; 0.01), and attenuated fibrosis (p &lt; 0.01) in MI mice. It downregulated myocardial phosphorylated Smad2/3, TGF-β1, and collagen deposition while upregulating SIRT1 (all p &lt; 0.01). In vitro, myricetin suppressed Ang II-induced fibrotic responses (Collagen I/III, MMP-2/9) (p &lt; 0.01) and migration (p &lt; 0.01). SIRT1 knockdown (shRNA) or EX527 treatment abolished myricetin's effects, restoring TGF-β1/p-Smad2/3 activity and collagen production i<i>n vitro</i> and in vivo.</p> Conclusion <p>Overall, myricetin attenuates post-MI cardiac fibrosis via SIRT1-dependent modulation of TGF-β1/Smad2/3 signaling, offering a translational potential for fibrosis-targeted therapy in heart failure.</p>

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Myricetin alleviates myocardial infarction-induced cardiac fibrosis in mice by upregulating SIRT1 to inhibit TGF-β1/Smad2/3 signaling

  • 期刊论文

  • 发表日期：

    2025年12月2日

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  • Xiaojv Xiong,
  • Rui Dai,
  • Guangji Wang,
  • Xin Guo,
  • Qin He,
  • Jijun Liu,
  • Gang Chen,
  • Pan Lu,
  • Shuang Li,
  • Denghai Liu,
  • Jinhua Liu,
  • Manhua Chen

摘要

Background

Myocardial infarction (MI) triggers adverse cardiac remodeling and fibrosis, leading to heart dysfunction. Myricetin, a natural flavonoid, has potential cardioprotective effects, but its mechanisms remain unclear. This study investigated whether myricetin alleviates MI-induced cardiac injury and fibrosis via SIRT1-mediated modulation of TGF-β1/Smad2/3 signaling.

Methods

A mouse MI model was established via left anterior descending (LAD) coronary artery ligation. Myricetin (100 mg/kg/day, oral gavage) was administered for 7 days pre-surgery, with the SIRT1 inhibitor EX527 (5 mg/kg, intraperitoneal) co-administered in subsets. Primary cardiac fibroblasts were pretreated with myricetin (5–30 μM) or SIRT1-targeted shRNA prior to angiotensin II (Ang II, 100 nM) exposure. Fibrosis, protein/mRNA expression, and cardiac function were assessed using histological (Masson's trichrome, TTC staining), molecular (Western blot, qPCR, immunofluorescence), and functional (echocardiography, transwell migration) analyses.

Results

Myricetin reduced infarct size (p < 0.01), improved cardiac function (decreased LVIDd/LVIDs, increased LVEF/LVFS) (p < 0.01), and attenuated fibrosis (p < 0.01) in MI mice. It downregulated myocardial phosphorylated Smad2/3, TGF-β1, and collagen deposition while upregulating SIRT1 (all p < 0.01). In vitro, myricetin suppressed Ang II-induced fibrotic responses (Collagen I/III, MMP-2/9) (p < 0.01) and migration (p < 0.01). SIRT1 knockdown (shRNA) or EX527 treatment abolished myricetin's effects, restoring TGF-β1/p-Smad2/3 activity and collagen production in vitro and in vivo.

Conclusion

Overall, myricetin attenuates post-MI cardiac fibrosis via SIRT1-dependent modulation of TGF-β1/Smad2/3 signaling, offering a translational potential for fibrosis-targeted therapy in heart failure.