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Objective <p>Dehydrodiisoeugenol (Deh) has demonstrated positive effects in the prevention and treatment of cardiovascular disease (CVD) caused by lipid overload, but its specific mechanism of action remains poorly understood. The aim of this study was to investigate the possible mechanisms by which Deh modulates the mitochondrial dysfunction induced by palmitate (PA) in vascular smooth muscle cells (VSMCs).</p> Methods <p>A PA-induced high-fat model of VSMCs was established, and the effect of PA on the VSMCs on function was detected by evaluating the oxidative stress and apoptosis of cells, as well as mitochondrial function. The expression of dynamin-related protein 1 (Drp1) was detected by immunofluorescence and immunoprecipitation. The key targets of Deh for the treatment of mitochondria-related diseases were screened by bioinformatics analysis and molecular docking techniques. Finally, the role of Silent information regulator 1 (SIRT1) in the treatment of PA-induced mitochondrial dysfunction in VSMCs by Deh was explored by administrating Deh as well as SIRT1 activator (CAY10602, CAY) and SIRT1 inhibitor (JGB1741, JGB).</p> Results <p>The results showed that PA concentration-dependently increased oxidative stress and apoptosis in VSMCs, while modulating the acetylation of Drp1, promoting its expression and mitochondrial ectopia, thereby inducing mitochondrial dysfunction. Bioinformatics analysis and molecular docking indicated that SIRT1 may be a key target of Deh for the treatment of mitochondria-related diseases. Follow-up experiments revealed that Deh significantly inhibited PA-induced mitochondrial dysfunction in VSMCs by suppressing acetylation and expression of Drp1 and reducing mitochondrial ectasia, an effect that was achieved by regulating SIRT1.</p> Conclusion <p>Deh was able to inhibit Drp1 expression and mitochondrial ectopia by reducing Drp1 acetylation through activation of SIRT1, thereby inhibiting PA-induced mitochondrial dysfunction effects in VSMCs, ameliorating pathological processes, such as cellular oxidative stress and apoptosis, and maintaining stable cellular functions.</p>

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Dehydrodiisoeugenol alleviates palmitate-induced mitochondrial dysfunction in human vascular smooth muscle cells through the activation of SIRT1-mediated Drp1 deacetylation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月24日

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  • Jianjun Zhao,
  • Zhiyun Shu,
  • Xiangjun Li,
  • Wenqing Zhang,
  • Mengze Sun,
  • Wenxiao Song,
  • Hongyuan Cheng,
  • Shaomin Shi

摘要

Objective

Dehydrodiisoeugenol (Deh) has demonstrated positive effects in the prevention and treatment of cardiovascular disease (CVD) caused by lipid overload, but its specific mechanism of action remains poorly understood. The aim of this study was to investigate the possible mechanisms by which Deh modulates the mitochondrial dysfunction induced by palmitate (PA) in vascular smooth muscle cells (VSMCs).

Methods

A PA-induced high-fat model of VSMCs was established, and the effect of PA on the VSMCs on function was detected by evaluating the oxidative stress and apoptosis of cells, as well as mitochondrial function. The expression of dynamin-related protein 1 (Drp1) was detected by immunofluorescence and immunoprecipitation. The key targets of Deh for the treatment of mitochondria-related diseases were screened by bioinformatics analysis and molecular docking techniques. Finally, the role of Silent information regulator 1 (SIRT1) in the treatment of PA-induced mitochondrial dysfunction in VSMCs by Deh was explored by administrating Deh as well as SIRT1 activator (CAY10602, CAY) and SIRT1 inhibitor (JGB1741, JGB).

Results

The results showed that PA concentration-dependently increased oxidative stress and apoptosis in VSMCs, while modulating the acetylation of Drp1, promoting its expression and mitochondrial ectopia, thereby inducing mitochondrial dysfunction. Bioinformatics analysis and molecular docking indicated that SIRT1 may be a key target of Deh for the treatment of mitochondria-related diseases. Follow-up experiments revealed that Deh significantly inhibited PA-induced mitochondrial dysfunction in VSMCs by suppressing acetylation and expression of Drp1 and reducing mitochondrial ectasia, an effect that was achieved by regulating SIRT1.

Conclusion

Deh was able to inhibit Drp1 expression and mitochondrial ectopia by reducing Drp1 acetylation through activation of SIRT1, thereby inhibiting PA-induced mitochondrial dysfunction effects in VSMCs, ameliorating pathological processes, such as cellular oxidative stress and apoptosis, and maintaining stable cellular functions.