2. Academic Validation
  3. Echinacoside ameliorates 5-fluorouracil-induced endothelial injury and senescence through SIRT1 activation

Echinacoside ameliorates 5-fluorouracil-induced endothelial injury and senescence through SIRT1 activation

  • Int Immunopharmacol. 2023 May 13;120:110279. doi: 10.1016/j.intimp.2023.110279.
Yiming Li 1,  Yingbiao Wu 2,  Zhongping Ning 3,  Xinming Li 4
Affiliations

Affiliations

  • 1 Department of Cardiology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China.
  • 2 Department of Cardiology, Shanghai Pudong New Area Zhoupu Hospital (Zhoupu Hospital affiliated with Shanghai Medical College of Health), Shanghai 201318, China.
  • 3 Department of Cardiology, Shanghai Pudong New Area Zhoupu Hospital (Zhoupu Hospital affiliated with Shanghai Medical College of Health), Shanghai 201318, China. Electronic address: [email protected].
  • 4 Department of Cardiology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, China; Department of Cardiology, Shanghai Pudong New Area Zhoupu Hospital (Zhoupu Hospital affiliated with Shanghai Medical College of Health), Shanghai 201318, China. Electronic address: [email protected].
PMID: 37187128 DOI: 10.1016/j.intimp.2023.110279
Abstract

Echinacoside (ECH) is a natural bioactive component with antioxidant, anti-inflammatory, anti-apoptosis, and anti-tumor properties. In the current study, we explore the ECH-mediated protective effect and underlying mechanism of 5-fluorouracil (5-FU)-induced endothelial injury and senescence in the Human umbilical vein endothelial cells (HUVECs). In HUVECs, Cell viability, Apoptosis and Senescence assays evaluated 5-fluorouracil-induced endothelial injury and senescence. Protein expressions were assessed using RT-qPCR and Western blotting. Our results showed that 5-FU-induced endothelial injury and endothelial cell senescence could be improved when treated with ECH in HUVECs. ECH treatment potentially attenuated oxidative stress and ROS production in HUVECs. In addition, the effect of ECH on Autophagy markedly reduced the percentage of HUVECs with LC3-II dots and suppressed the Beclin-1 and ATG7 mRNA expression but enhanced the p62 mRNA expression. Besides, ECH treatment significantly increased migrated cells and suppressed the adhesion of THP-1 monocytes in HUVECs. Furthermore, ECH treatment activated the SIRT1 pathway, and its related proteins (SIRT1, p-AMPK and eNOS) expression increased. Nicotinamide (NAM), an inhibitor of SIRT1, significantly attenuated the ECH-induced decrease in the apoptotic rate, increased SA-β-gal-positive cells and significantly reversed the ECH-induced reduction of endothelial senescence. Our results demonstrated that ECH employed endothelial injury and senescence in HUVECs via activation of the SIRT1 pathway.

Keywords

5-fluorouracil; Autophagy; Echinacoside; Endothelial injury; Senescence.

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