biostudies-literatureXia QNatural Science Foundation of Shandong ProvinceChina Postdoctoral Science FoundationThe Young Scientists Fund of the National Natural Science Foundation of China2https://www.ebi.ac.uk/biostudies/studies/S-EPMC12657559biostudies-literatureUnknown51(1)Neuronal cell damage resulting from ischemic and hypoxic injury is a major pathological event in stroke, with ferroptosis increasingly recognized as a contributing mechanism. In this study, we observed that oxygen-glucose deprivation (OGD) triggered ferroptosis in neuronal cells. By screening of naphthoquinone compounds intervening oxidative stress, we have identified phylloquinone (VK1, also known as vitamin K1) as a potent inhibitor of ferroptosis with significant neuroprotective effects. Phylloquinone also alleviated OGD-induced cellular senescence. Mechanistic investigation revealed that Kruppel-like factor 2 (Klf2) is a potential target of phylloquinone and participates in its neuroprotective effects. These findings indicate that phylloquinone protects neurons from OGD-induced injury Neurochemical researchPhylloquinone Attenuates Oxygen-Glucose Deprivation-induced Neuronal Injury by Inhibiting Ferroptosis via the xCT/GPX4 Pathway.PMC126575592024M751849ZR202211220007NO. 82403338Li YLiu ZHe DXia QLi LWang ZfalsePhylloquinone Attenuates Oxygen-Glucose Deprivation-induced Neuronal Injury by Inhibiting Ferroptosis via the xCT/GPX4 Pathway.Neuronal cell damage resulting from ischemic and hypoxic injury is a major pathological event in stroke, with ferroptosis increasingly recognized as a contributing mechanism. In this study, we observed that oxygen-glucose deprivation (OGD) triggered ferroptosis in neuronal cells. By screening of naphthoquinone compounds intervening oxidative stress, we have identified phylloquinone (VK1, also known as vitamin K1) as a potent inhibitor of ferroptosis with significant neuroprotective effects. Phylloquinone also alleviated OGD-induced cellular senescence. Mechanistic investigation revealed that Kruppel-like factor 2 (Klf2) is a potential target of phylloquinone and participates in its neuroprotective effects. These findings indicate that phylloquinone protects neurons from OGD-induced injury 2025-01-01T00:00:00Z2025 Nov2026-06-05T21:33:24.131Z2026-05-22T03:11:42.682ZS-EPMC126575594129610810.1007/s11064-025-04616-3