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

Coronary heart disease (CHD) is a disease caused by organic and functional coronary artery stenosis, resulting in a reduced oxygen supply to the heart. This study aimed to investigate the mechanism via which Luteolin regulates the Sirt1 / Nrf2 pathway to inhibit ferroptosis in human umbilical vein endothelial cells (HUVEC) associated with CHD. An ox-LDL-induced HUVEC cell model with Sirt1 silencing and Luteolin treatment was established. The silencing efficiency of Sirt1 was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The results of molecular docking and DARTS experiments showed that Luteolin could effectively bind Sirt1 . Subsequently, we measured the expression of Nrf2 and Sirt1 , cell viability, MDA, GSH, Fe 2+ levels, lipid ROS content, expression of ferroptosis-related proteins GPX4, FTH, FTL, and cell migration parameters. The results showed that Luteolin could activate the Sirt1 / Nrf2 axis and effectively inhibit ox-LDL-induced ferroptosis in HUVEC. Experimental results revealed that Luteolin could enhance HUVEC cell viability, decrease MDA, Fe 2+ , and ROS levels, increase GSH levels, promote the expression of HO-1, GPX4, FTH, FTL, inhibit the expression of ACSL4 and TFRC, and enhance the migration capability of HUVEC cells. Moreover, silencing Sirt1 reversed the effects of Luteolin on the activation of Sirt1 and Nrf2 , confirming the dependence of these effects on the Sirt1 / Nrf2 signaling pathway. In conclusion, this study indicates that Luteolin could inhibit ferroptosis in HUVEC in CHD by modulating the Sirt1 / Nrf2 axis, providing a basis for further research on strategies for preventing and treating CHD and related diseases.