Quercetin alleviates endothelial dysfunction in preeclampsia by inhibiting ferroptosis and inflammation through EGFR binding

Meiting Shi; Lu Sun; Jiachun Wei; Yao Shen; Jian Wang; Ping Zhang; Xiaofeng Yang; Yuzhen Ding; Wanchang Yin; Xinyao Lu; Xuesong Yang; Guang Wang; Ruiman Li

doi:10.1038/s42003-025-07547-5

Quercetin alleviates endothelial dysfunction in preeclampsia by inhibiting ferroptosis and inflammation through EGFR binding

Commun Biol. 2025 Jan 20;8(1):90. doi: 10.1038/s42003-025-07547-5.

Authors

Meiting Shi^#^{1

2}, Lu Sun^#¹, Jiachun Wei^#¹, Yao Shen^{2

3}, Jian Wang¹, Ping Zhang¹, Xiaofeng Yang¹, Yuzhen Ding¹, Wanchang Yin¹, Xinyao Lu¹, Xuesong Yang^{4

5

6}, Guang Wang^{7

8

9}, Ruiman Li¹⁰

Affiliations

¹ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
² International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, China.
³ Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China.
⁴ International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, China. [email protected].
⁵ Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China. [email protected].
⁶ Clinical Research Center, Clifford Hospital, Guangzhou, China. [email protected].
⁷ International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, China. [email protected].
⁸ Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou, China. [email protected].
⁹ Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Guangdong Second Provincial General Hospital, School of Medicine, Jinan University, Guangzhou, China. [email protected].
¹⁰ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China. [email protected].

^# Contributed equally.

PMID: 39833490
DOI: 10.1038/s42003-025-07547-5

Abstract

Preeclampsia (PE) is a pregnancy-specific complication and there remains no effective treatment. Given the limitations on medication use during pregnancy, exploring natural, safe, and effective drugs for PE is worthwhile. We investigate the causal relationship between ferroptosis, inflammation, and PE, and determine the protective effects of quercetin (QCT), a representative compound that is classified as a flavanol, against endothelial dysfunction. Then, the target of QCT is predicted and verified. The prophylactic addition of a low dose of QCT rescues endothelial dysfunction, aiding in endothelial repair. Furthermore, QCT alleviates PE-like maternal manifestations and endothelial dysfunction in the placenta of the selective reduced uteroplacental perfusion (sRUPP) rat model through binding to the epidermal growth factor receptor (EGFR). The potential applications of QCT are expanded, offering the possibility of further development as a safe and effective preventive molecule for PE.

MeSH terms

Animals
Disease Models, Animal
ErbB Receptors* / metabolism
Female
Ferroptosis* / drug effects
Humans
Inflammation* / drug therapy
Inflammation* / metabolism
Pre-Eclampsia* / drug therapy
Pre-Eclampsia* / metabolism
Pregnancy
Quercetin* / pharmacology
Rats
Rats, Sprague-Dawley

Substances

Quercetin
ErbB Receptors
Egfr protein, rat