Evidence map›Paper›PMID 42240802›Full record

ArticleMolecular neurobiology2026

Dl‑3‑n‑Butylphthalide Protects the Blood-Brain Barrier in Neonatal Hypoxic‑Ischemic Brain Damage by Alleviating Endothelial Cell Ferroptosis via the SLC7A11/GSH/GPX4 Pathway.

Jiahao Ou, Qianqian Yu, Yuqi Luo, Ming Shen, Jia Lou, Saizhi Jiang, BangMing Ye, LiZi Lin, Jianghu Zhu, Zhenlang Lin and 1 more

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Jiahao Ou *Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Qianqian Yu *Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yuqi Luo *Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Ming ShenDepartment of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jia LouDepartment of Pediatrics, Dongyang People's Hospital, Dongyang, Zhejiang, China.
Saizhi JiangDepartment of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
BangMing YeDepartment of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
LiZi LinDepartment of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jianghu ZhuDepartment of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zhenlang LinDepartment of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. linzhenlang@hotmail.com.
Mingchu FangDepartment of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. fangmingchu@wmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxic-ischemic brain damage (HIBD) is a major contributor to neurological disabilities. Our previous studies have demonstrated that DL-3-n-butylphthalide (NBP) confers protective effects against HIBD and mitigates blood-brain barrier (BBB) impairment, but the underlying mechanism remains unclear. This study aimed to investigate the mechanism by which NBP protects against ferroptosis-induced BBB damage. Our results showed that NBP treatment significantly reduced infarct volume (by 24.09%), alleviated cerebral edema (brain water content decreased by 1.651%), attenuated BBB disruption, suppressed neuroinflammation, promoted neuronal repair, and improved functional recovery. Using RNA sequencing, molecular docking, and surface plasmon resonance (SPR) assays, we discovered for the first time that NBP directly binds to membrane-bound SLC7A11 with a KD value of 222.0 µM, thereby activating the SLC7A11/GSH/GPX4 pathway and inhibiting ferroptosis in cerebrovascular endothelial cells. Different from previously reported anti-apoptotic and anti-inflammatory mechanisms of NBP, the present study reveals a novel mechanism by which NBP protects the BBB through inhibiting endothelial ferroptosis. The protective effect of NBP was further validated by knocking down SLC7A11 with specific siRNA, confirming its dependence on SLC7A11. Ultimately, NBP ameliorated BBB damage both in vitro and in vivo. In summary, NBP attenuates BBB disruption by targeting the SLC7A11/GSH/GPX4 pathway and inhibiting endothelial ferroptosis, thereby reducing brain injury and promoting neural recovery.

Indexed as

Amino Acid Transport System y+BenzofuransBlood-Brain BarrierEndothelial CellsFerroptosisGlutathioneHypoxia-Ischemia, BrainNeuroprotective AgentsAnimalsAnimals, NewbornSignal Transduction3-n-butylphthalideAmino Acid Transport System y+BenzofuransGlutathioneNeuroprotective AgentsBlood-brain barrierDL-3-n-butylphthalideEndothelial cellsFerroptosisHypoxic-ischemic brain damageSLC7A11/GSH/GPX4

Identifiers

PMID42240802

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.