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Background <p>Myocardial infarction (MI) is a life-threatening coronary-related pathology. Betulinic acid (BA) has been revealed to have beneficial effects on cardiac disease through its role in modulating multiple mechanisms. This study aimed to investigate whether BA can alleviate cardiac remodeling after MI and elucidate the possible signaling mechanisms behind its regulation.</p> Methods <p>A MI rat model was established by ligating the left anterior descending coronary artery (LAD). Following surgery, rats were treated with 10 or 30&#xa0;mg/kg BA for 30&#xa0;days. Survival analysis, echocardiographic analysis, heart wight, Masson’s trichrome staining, hematoxylin–eosin staining, 2,3,5-triphenyltetrazolium chloride staining, RT-qPCR, western blotting, terminal-deoxynucleoitidyl transferase-mediated nick end labeling staining, and dihydroethidium staining were performed to evaluate the BA’s cardioprotective effects after MI. H9C2 cells were pretreated with BA and cultured under the hypoxia condition. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, 2′,7′-Dichlorofluorescein diacetate staining, RT-qPCR, and western blotting were used to validate the antioxidant, anti-apoptotic, and anti-inflammatory effects of BA in hypoxia-stimulated H9C2 cells.</p> Results <p>BA improved the survival rate and left ventricular function in rats after MI. BA reduced the size of infarction and the cross-sectional area of cardiomyocytes. BA reduced the fibrotic area in the hearts of MI rats, accompanied by downregulation of fibrotic markers and fibrosis signaling-related proteins. BA also inhibited inflammatory response, oxidative stress, and apoptosis in MI rat models and hypoxia-stimulated H9C2 cells. In rescue assays, inhibition of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) reversed the effects of BA in hypoxia-stimulated H9C2 cells. BA activated Nrf2 signaling by enhancing sirtuin1 (SIRT1) expression.</p> Conclusion <p>In conclusion, this study shows a novel finding that BA ameliorates adverse cardiac remodeling following MI through activation of Sirt1/Nrf2 signaling.</p>

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Betulinic acid alleviates cardiac fibrosis and dysfunction in rats after myocardial infarction by activating the Sirt1/Nrf2 pathway

  • 期刊论文

  • 发表日期：

    2025年4月10日

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  • Rong Tan,
  • Yunchao Deng,
  • Mengmeng Deng,
  • Bo Liu

摘要

Background

Myocardial infarction (MI) is a life-threatening coronary-related pathology. Betulinic acid (BA) has been revealed to have beneficial effects on cardiac disease through its role in modulating multiple mechanisms. This study aimed to investigate whether BA can alleviate cardiac remodeling after MI and elucidate the possible signaling mechanisms behind its regulation.

Methods

A MI rat model was established by ligating the left anterior descending coronary artery (LAD). Following surgery, rats were treated with 10 or 30 mg/kg BA for 30 days. Survival analysis, echocardiographic analysis, heart wight, Masson’s trichrome staining, hematoxylin–eosin staining, 2,3,5-triphenyltetrazolium chloride staining, RT-qPCR, western blotting, terminal-deoxynucleoitidyl transferase-mediated nick end labeling staining, and dihydroethidium staining were performed to evaluate the BA’s cardioprotective effects after MI. H9C2 cells were pretreated with BA and cultured under the hypoxia condition. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, 2′,7′-Dichlorofluorescein diacetate staining, RT-qPCR, and western blotting were used to validate the antioxidant, anti-apoptotic, and anti-inflammatory effects of BA in hypoxia-stimulated H9C2 cells.

Results

BA improved the survival rate and left ventricular function in rats after MI. BA reduced the size of infarction and the cross-sectional area of cardiomyocytes. BA reduced the fibrotic area in the hearts of MI rats, accompanied by downregulation of fibrotic markers and fibrosis signaling-related proteins. BA also inhibited inflammatory response, oxidative stress, and apoptosis in MI rat models and hypoxia-stimulated H9C2 cells. In rescue assays, inhibition of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) reversed the effects of BA in hypoxia-stimulated H9C2 cells. BA activated Nrf2 signaling by enhancing sirtuin1 (SIRT1) expression.

Conclusion

In conclusion, this study shows a novel finding that BA ameliorates adverse cardiac remodeling following MI through activation of Sirt1/Nrf2 signaling.