2. Academic Validation
  3. Berberine inhibits high glucose-induced ferroptosis in retinal vascular endothelial cells: Mechanism and implications

Berberine inhibits high glucose-induced ferroptosis in retinal vascular endothelial cells: Mechanism and implications

  • Exp Eye Res. 2025 Oct:259:110531. doi: 10.1016/j.exer.2025.110531.
Jia Chen 1,  Wenxuan Peng 1,  Wen Yang 1,  Zhipeng You 1,  Yuling Zou 2
Affiliations

Affiliations

  • 1 The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, Jiangxi Province Key Laboratory of Ophthalmology and Vision Sciences, Jiangxi Clinical Research Center for Ophthalmic Disease, Jiangxi Provincial Key Laboratory of Vitreoretinal Diseases for Health, Jiangxi Province, Nanchang, 330006, China.
  • 2 The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, Jiangxi Province Key Laboratory of Ophthalmology and Vision Sciences, Jiangxi Clinical Research Center for Ophthalmic Disease, Jiangxi Provincial Key Laboratory of Vitreoretinal Diseases for Health, Jiangxi Province, Nanchang, 330006, China. Electronic address: Zouyuling51@163.com.
PMID: 40701537 DOI: 10.1016/j.exer.2025.110531
Abstract

This study investigates Ferroptosis in human retinal microvascular endothelial cells (HRMECs) under high-glucose conditions and explores the therapeutic potential of Berberine (BBR) in mitigating this process. Using Western blotting and RT-qPCR, we observed that prolonged high glucose (48 h) significantly downregulated GPX4 and FSP1 protein levels, reduced GPX4 mRNA expression, and elevated ACSL4 protein levels, indicative of Ferroptosis induction. BBR intervention reversed these effects, upregulating Nrf2, HO-1, GPX4, and FSP1 while suppressing ACSL4. Mechanistically, BBR attenuated oxidative stress by reducing ROS, lipid peroxidation (MDA), and Fe2+ accumulation, as demonstrated via fluorescence microscopy, GSH/MDA assays, and transmission electron microscopy, which revealed preserved mitochondrial integrity in BBR-treated cells. CCK-8 assays confirmed BBR's role in restoring HRMEC viability under high glucose. These findings highlight BBR's ability to inhibit Ferroptosis through the Nrf2/HO-1/GPX4 pathway, offering novel insights into diabetic retinopathy (DR) pathogenesis and suggesting BBR as a promising therapeutic candidate to delay DR progression.

Keywords

Berberine; Diabetic retinopathy; Ferroptosis; Oxidative stress; Retinal microvascular endothelial cells.

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