Luteolin Inhibits Ferroptosis of HUVEC by Regulating the Sirt1/Nrf2 Pathway

Ming Xiang1,2, Xiangdong Lin3, Haiying Chen4

  • 1Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, China.

Insights

Luteolin inhibits ferroptosis in coronary heart disease (CHD) by activating the Sirt1/Nrf2 pathway in human umbilical vein endothelial cells (HUVEC). This finding offers new therapeutic strategies for CHD.

Area of Science:

  • Biomedical research
  • Cardiovascular science
  • Molecular biology

Background:

  • Coronary heart disease (CHD) involves coronary artery stenosis, reducing heart oxygen supply.
  • Ferroptosis, a regulated cell death, plays a role in endothelial cell dysfunction in CHD.
  • Luteolin is a flavonoid with potential therapeutic properties.

Purpose of the Study:

  • To investigate Luteolin's mechanism in inhibiting ferroptosis in CHD-associated human umbilical vein endothelial cells (HUVEC).
  • To determine Luteolin's regulation of the Sirt1/Nrf2 pathway in this context.

Main Methods:

  • Established an ox-LDL-induced HUVEC model with Sirt1 silencing and Luteolin treatment.
  • Validated Sirt1 silencing using qRT-PCR and Western blot.
  • Performed molecular docking and DARTS assays to confirm Luteolin-Sirt1 binding.
  • Assessed cell viability, ferroptosis markers (MDA, GSH, Fe2+, ROS, GPX4, FTH, FTL), and cell migration.

Main Results:

  • Luteolin activated the Sirt1/Nrf2 axis and inhibited ox-LDL-induced ferroptosis in HUVEC.
  • Luteolin enhanced cell viability, increased GSH levels, and promoted ferroptosis suppressor expression (HO-1, GPX4, FTH, FTL).
  • Luteolin decreased MDA, Fe2+, ROS levels, inhibited ferroptosis inducers (ACSL4, TFRC), and improved cell migration.
  • Sirt1 silencing reversed Luteolin's protective effects, confirming pathway dependence.

Conclusions:

  • Luteolin inhibits ferroptosis in HUVEC in CHD by modulating the Sirt1/Nrf2 pathway.
  • This study provides a mechanistic basis for Luteolin as a potential therapeutic agent for CHD.
  • Further research into Luteolin-based strategies for CHD prevention and treatment is warranted.

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