Related Experiment Video
Updated: Sep 13, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
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.
Abstract:
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, Fe2+ 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, Fe2+, 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.
Related Concept Videos
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
The Unfolded Protein Response
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....

