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Published on: July 13, 2018
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.
Abstract:
Our previous studies have highlighted the potential therapeutic efficacy of dendrobine, an alkaloid, in atherosclerosis (AS), nevertheless, the underlying mechanism remains unclear. This study employs a combination of network pharmacology and in vitro experiments to explore the regulatory pathways involved. Through network pharmacology, the biological function for intersection targets between dendrobine and AS were identified. Molecular docking was conducted to investigate the interaction between the dominant target and dendrobine. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic AS, and the effects of dendrobine on cell viability, lipid deposition, mitochondrial function, and cellular senescence were evaluated. Subsequently, cells were treated with the mitophagy inhibitor Mdivi-1 and the STAT3 agonist colivelin to assess the role of mitophagy and STAT3 signaling in dendrobine regulation. Intersection targets were associated with biological processes, including reactive oxygen species production. Dendrobine attenuated the effects of ox-LDL treatment on HUVECs, mitigating changes in cell activity, lipid deposition, mitochondrial function, and cellular senescence. Both Mdivi-1 and colivelin treatments resulted in decreased cell viability and increased cellular senescence, with colivelin suppressing mitophagy. Cotreatment with Mdivi-1 and colivelin further aggravated cellular senescence and inhibited FoxO signaling. Together, this study indicated that dendrobine regulated the STAT3/FoxO signaling pathway, alleviating mitochondrial dysfunction and cellular senescence. This study contributes valuable insights to the potential clinical application of dendrobine.
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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