Aug 2026· Experimental Eye Research· Vol 272, pp.
111214
· 0 citations· 58 references
Medicine
TL;DR
Findings suggest that EGCG alleviates RPE damage associated with NF-κB p65-mediated ferroptosis, providing new insights into AMD pathogenesis and a promising therapeutic strategy.
Abstract
The accumulation of ferrous ions and resulting oxidative stress within the retinal pigment epithelium triggers ferroptosis, leading to photoreceptor degeneration in dry age-related macular degeneration (dAMD), which is a disease currently without effective therapy. As ferroptosis has been identified as a molecular target of epigallocatechin-3-gallate (EGCG) in other diseases, this study aimed to investigate the protective role of EGCG and its mechanism against ferroptosis in NaIO3-induced ARPE-19 cell and RPE injury. We observed that iron overload disrupts iron homeostasis in both cellular and animal models, leading to RPE damage via ferroptosis activation. In ARPE-19 cells, EGCG attenuated NaIO3-induced injury by reducing Fe2+, MDA, and LDH levels, increasing GSH content, and upregulating SLC7A11 and GPX4 expression, effects which were equivalent to those produced by Fer-1. Mechanistically, EGCG exerted its anti-ferroptotic effect by binding strongly to NF-κB p65 and inhibiting its activation, consistent with the effects of the NF-κB inhibitor QNZ and NF-κB p65 silencing. In a dAMD model, EGCG administration suppressed ferroptosis, downregulated NF-κB p65 expression, and ameliorated RPE damage. In conclusion, these findings suggest that EGCG alleviates RPE damage associated with NF-κB p65-mediated ferroptosis, providing new insights into AMD pathogenesis and a promising therapeutic strategy.
Investigating the potential role of the RNA-binding protein human antigen R (HuR) in mediating ferroptosis during DR progression, as well as the protective effects of Procyanidin C1 (PC1), demonstrated that PC1 significantly alleviated oxidative stress and ferroptosis in both diabetic mice and high-glucose-treated BV2s.
Qun Liu, Song-Min Wang, Tao Jiao et al.· Experimental Eye Research· 0 citations
Artemisinin (ART) is known to alleviate inflammation in mastitis, but its effect on ferroptosis in mammary epithelial cells and the associated regulatory mechanisms has not been fully clarified. Here, we demonstrate that ART markedly attenuates inflammatory injury and ferroptosis in Staphylococcus aureus-induced mastitis models both in vivo and in vitro. ART treatment reduces iron accumulation and lipid peroxidation while restoring antioxidant capacity, accompanied by improved mitochondrial integrity. Mechanistically, ART upregulates the palmitoyltransferase ZDHHC12, which promotes palmitoylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and facilitates its nuclear translocation. Activation of Nrf2 subsequently enhances heme oxygenase-1 (HO-1) signaling, leading to suppression of inflammation and ferroptosis. Collectively, these findings reveal that ART exerts protective effects against mastitis by activating the ZDHHC12/Nrf2/HO‑1 axis, highlighting ART as a potential therapeutic agent for mastitis through coordinated inhibition of inflammation and ferroptosis.
Zeqiu Fan, Yang Luo, Zhenzhao Zhang et al.· Communications Biology· 0 citations
Chronic exposure to lead (Pb) represents a persistent environmental hazard that can impair hippocampal integrity and cognitive function, while effective protective strategies remain limited. Ginsenoside Rg1 is an important bioactive constituent derived from Panax ginseng and has been reported to possess antioxidant and neuroprotective activities; however, its involvement in Pb-triggered ferroptosis-associated neuronal damage remains unclear. In the present study, a male C57BL/6J mouse model of subchronic lead acetate exposure and a lead-exposed HT22 cell model were established. Behavioral and histopathological changes were assessed, followed by analysis of inflammatory responses, oxidative stress, ferroptosis-related alterations, and Nrf2-associated signaling. Rg1 improved cognitive performance and attenuated hippocampal neuronal loss, neuroinflammatory activation, oxidative injury, and ferroptosis-related alterations, including ferrous ion accumulation and mitochondrial damage. Consistently, Rg1 restored SLC7A11/xCT and GPX4 expression and enhanced Nrf2-associated antioxidant signaling, whereas the Nrf2 inhibitor ML385 weakened the Rg1-induced increases in nuclear Nrf2, NQO1, and GPX4. Collectively, these findings indicate that Rg1 alleviates lead-induced neurotoxicity and support the involvement of Nrf2 signaling in the regulation of oxidative stress and ferroptosis-related injury. These findings provide experimental evidence supporting further preclinical investigation of Rg1 and its Nrf2-associated neuroprotective mechanisms in Pb-induced neuronal injury.
Yiyao Gong, Jie Zhang, Tingting Wang et al.· Molecules· 0 citations
Eugenol exerts neuroprotective effects in glaucoma excitotoxicity models by suppressing ferroptosis through Mfn2-mediated regulation of mitochondrial-LD homeostasis and the SLC7A11/GSH/GPX4 antioxidant pathway.
Qian Wang, Lemeng Feng, Cheng Zhang et al.· Molecular and Cellular Bioch...· 0 citations
EGb 761 exerts a protective effect on photoreceptor cell damage in retinal degeneration and is associated with a modification of the AMPK/ERK signaling pathway that regulates oxidative stress and autophagy.
Qiu-ye Teng, M. Chudhary, Wenkang Dong et al.· Current Eye Research· 0 citations
Endothelial cell ferroptosis drives atherosclerosis. Salvianolic acid A (SAA), a polyphenol from Salvia species, was tested for its ability to inhibit ferroptosis and attenuate atherosclerosis, and its molecular mechanism was investigated. Screening of 124 natural compounds identified SAA as the most potent inhibitor of RSL3-induced ferroptosis in human umbilical vein endothelial cells (HUVECs). Cellular/mitochondrial lipid peroxidation, Fe2+ content, ROS, and mitochondrial function were assessed with or without SAA. AMPK signaling was probed using pharmacological inhibitors. The AdipoR1 axis was examined via siRNA knockdown. In vivo, ApoE-/- mice on a Western diet were treated with SAA to evaluate atherosclerosis and ferroptotic damage. SAA was identified as the most potent inhibitor of (1S,3R)-RSL3-induced ferroptosis in HUVECs among the screened natural compounds. SAA inhibited the ferroptotic response by restoring GPX4-dependent antioxidant capacity and preventing lipid peroxidation at both the cellular and mitochondrial levels. It improved mitochondrial function by restoring homeostasis of the mitochondrial quality control system, inhibiting mitochondrial reactive oxygen species generation, reducing ferrous iron accumulation, limiting mitochondrial lipid peroxidation, and preserving mitochondrial ultrastructure. The protective effects of SAA against ferroptosis were abolished by AMPK inhibitors, which disrupted cellular lipid metabolism and mitochondrial function regulation. The deleterious effects of AMPK inhibition were reversed by co-treatment with the mitochondrial reactive oxygen species inhibitor MitoTempol. Knockdown of AdipoR1 and experiments with the AMPK agonist AICAR confirmed that salvianolic acid A restores mitochondrial homeostasis and inhibits ferroptosis specifically through activation of the AdipoR1-AMPK signaling pathway. In vivo, treatment with SAA significantly ameliorated Western diet-induced atherosclerosis and ferroptosis-like cell damage in ApoE-/- mice. SAA has strong therapeutic potential against endothelial ferroptosis and atherosclerosis by restoring mitochondrial homeostasis through AdipoR1-AMPK pathway activation. These findings support further clinical investigation of SAA for treating atherosclerosis and other endothelium-related cardiovascular diseases.
Ji Zhu, Jianan Guo, Jing Liu et al.· Phytotherapy Research· 0 citations
