Jul 2026· Molecular and Cellular Biochemistry· 0 citations· 42 references
Medicine
TL;DR
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.
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
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.
Xiao-Yang Chen, Miao Han, Yi-Wen An et al.· Experimental Eye Research· 0 citations
BACKGROUND
Cerebral ischemia-reperfusion injury (CIRI) is a devastating neurological disorder involving autophagy, oxidative stress, and ferroptosis. Tetramethylpyrazine (TMP) has demonstrated potential pharmacological efficacy in antiplatelet aggregation, antithrombotic effects, vasodilation, and neuroprotection.
PURPOSE
This study aimed to determine the therapeutic efficacy of TMP in treating CIRI and to investigate whether TMP could improve CIRI by inhibiting ferroptosis through activation of the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1)/glutathione Peroxidase 4 (GPX4) pathway in rats.
METHODS
We established MCAO/R rat models and OGD/R-treated HT22 cell models to evaluate the neuroprotective effects of TMP, employed network pharmacology and metabolomics to predict key signaling pathways, and assessed ferroptosis-related changes via biochemical assays, Western blotting, and transmission electron microscopy.
RESULTS
In vivo studies showed that TMP improved neurological scores, reduced infarct volume, and mitigated pathological features following MCAO/R. Network pharmacology and metabolomics revealed that TMP indirectly activated NRF2-mediated antioxidant responses while regulating glycerophospholipid metabolism and glycine/serine/threonine metabolism pathways. Mechanistically, TMP reduced oxidative stress markers, restored antioxidant capacity, and upregulated NRF2, HO-1, GPX4 and SLC7A11 expression, while the NRF2 inhibitor ML385 reversed these effects. These findings were further corroborated by in vitro experiments in OGD/R-exposed HT22 neurons, where TMP enhanced cell viability, attenuated lipid peroxidation and iron accumulation, and preserved mitochondrial ultrastructure, with ML385 partially reversing the protective effects.
CONCLUSION
TMP exerts neuroprotective effects in mitigating CIRI, which is associated with the regulation of ferroptosis and involves activation of the NRF2/HO-1/GPX4 pathway.
Hengpei Gong, Yinjun Lu, Lingfeng Wang et al.· Tissue & Cell· 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
AIM
To investigate the protective effects of deferoxamine (DFO) on high glucose (HG)-induced ferroptosis and inflammatory responses in retinal Müller glial cells (MGCs) and offer potential therapeutic targets for early intervention in diabetic retinopathy (DR).
METHODS
Primary MGCs were cultured from C57BL/6J mouse retinas and exposed to normal glucose (NG, 5 mmol/L) or HG (25 mmol/L) conditions for various durations. Ferroptosis-related markers, including intracellular Fe2+ levels, glutathione (GSH), reactive oxygen species (ROS), malondialdehyde (MDA), and key proteins glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), were examined using multiple assays such as immunoblotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF), and fluorometric detection. The role of DFO was evaluated through cell viability assessment and analysis of inflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α).
RESULTS
HG exposure significantly increased intracellular Fe2+ content, decreased GSH levels, elevated ROS and MDA concentrations, and altered expression profiles of ferroptosis regulators GPX4 and SLC7A11. Immunoblot and IF analyses confirmed downregulation of GPX4 and SLC7A11 alongside accumulation of FTH1 under prolonged HG treatment. DFO administration markedly attenuated these ferroptotic changes while reducing inflammatory cytokine secretion, demonstrating its protective effect against HG-induced damage in MGCs by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/thioredoxin reductase 1 (TXNRD1) pathway.
CONCLUSION
Low-dose DFO effectively mitigates HG-induced ferroptosis and inflammatory responses in MGCs through the Nrf2/TXNRD1 signaling axis, providing a theoretical framework for developing novel therapeutic strategies in DR management.
Min Luo, Yi Zhang, Na Li et al.· International Journal of Oph...· 0 citations
It is demonstrated that BPA activates the AMPK/mTOR/ULK1 signaling pathway to promote NCOA4‑mediated ferritinophagy, leading to ferroptosis in HT‑22 cells.
Yue Zhang, Yuxin Wang, Ping He et al.· Toxicology Letters· 0 citations
