Dendrobine regulates STAT3 to attenuate mitochondrial dysfunction and senescence in vascular endothelial cells

Jia Xia1, Jingyi Chen2, Xinyue Xing2

  • 1Department of Rheumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Drug Development Research
|February 13, 2024
PubMed

Insights

Dendrobine shows therapeutic potential for atherosclerosis by regulating the STAT3/FoxO pathway. This mechanism alleviates mitochondrial dysfunction and cellular senescence, offering insights for clinical applications.

Area of Science:

  • Pharmacology and Molecular Biology
  • Cardiovascular Research

Background:

  • Dendrobine exhibits potential therapeutic effects in atherosclerosis (AS).
  • The precise molecular mechanisms underlying dendrobine's action in AS are not fully understood.

Purpose of the Study:

  • To elucidate the regulatory pathways of dendrobine in atherosclerosis using network pharmacology and in vitro experiments.
  • To investigate the role of mitophagy and STAT3 signaling in dendrobine's therapeutic effects.

Main Methods:

  • Network pharmacology identified intersection targets between dendrobine and AS.
  • Molecular docking assessed the interaction between dendrobine and its dominant target.
  • In vitro experiments utilized oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs) to evaluate dendrobine's effects.
  • Mitophagy inhibitor (Mdivi-1) and STAT3 agonist (colivelin) were used to probe signaling pathways.

Main Results:

  • Dendrobine treatment attenuated ox-LDL-induced detrimental effects on HUVECs, including improved cell viability, reduced lipid deposition, enhanced mitochondrial function, and mitigated cellular senescence.
  • STAT3 signaling and mitophagy were identified as key pathways regulated by dendrobine.
  • Dendrobine's effects were linked to the regulation of the STAT3/FoxO signaling pathway.

Conclusions:

  • Dendrobine effectively alleviates mitochondrial dysfunction and cellular senescence in an atherosclerosis model.
  • The study highlights the STAT3/FoxO signaling pathway as a crucial mediator of dendrobine's therapeutic action.
  • Findings provide a mechanistic basis for the potential clinical application of dendrobine in treating atherosclerosis.

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