2. Academic Validation
  3. Phylloquinone Attenuates Oxygen-Glucose Deprivation-induced Neuronal Injury by Inhibiting Ferroptosis via the xCT/GPX4 Pathway

Phylloquinone Attenuates Oxygen-Glucose Deprivation-induced Neuronal Injury by Inhibiting Ferroptosis via the xCT/GPX4 Pathway

  • Neurochem Res. 2025 Nov 26;51(1):2. doi: 10.1007/s11064-025-04616-3.
Qian Xia 1,  Longji Li 2,  Yuchen Li 2,  Zhihai Wang 2,  Dong He 3 4,  Zihao Liu 5 6
Affiliations

Affiliations

  • 1 Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
  • 2 Department of Neurosurgery, Shandong Qianfoshan Hospital, Shandong University, Jinan, 250014, China.
  • 3 Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China. [email protected].
  • 4 Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China. [email protected].
  • 5 Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China. [email protected].
  • 6 Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China. [email protected].
PMID: 41296108 DOI: 10.1007/s11064-025-04616-3
Abstract

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 by inhibiting Ferroptosis through the xCT/GPX4 pathway, highlighting its potential as a therapeutic candidate for ischemic neuronal damage.

Keywords

Ferroptosis; Neuroprotection; Oxygen-glucose deprivation; Phylloquinone.

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