Evidence map›Paper›PMID 41545774›Full record

ArticleMolecular neurobiology2026

3-n-Butylphthalide Protects SH-SY5Y Cells from Ferroptosis by Inhibiting ACSL4-Mediated Lipid Peroxidation.

Huanhuan Wei, Yiyin Zhang, Qianqian Ju, Bolin Lian, Tong Gao, Haiqin Duan, Xiang Yin, Yongqi Lin, Jianhong Shen, Qiuhong Ji and 2 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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Huanhuan WeiDepartment of Neurology, Affiliated Hospital of Nantong University, Nantong, China.
Yiyin ZhangDepartment of Neurology, Affiliated Hospital of Nantong University, Nantong, China.
Qianqian JuJiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Bolin LianSchool of Life Sciences, Nantong University, Nantong, China.
Tong GaoDepartment of Neurology, Affiliated Hospital of Nantong University, Nantong, China.
Haiqin DuanDepartment of Neurology, Affiliated Hospital of Nantong University, Nantong, China.
Xiang YinJiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Yongqi LinJiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Jianhong ShenDepartment of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, China.
Qiuhong JiDepartment of Neurology, Affiliated Hospital of Nantong University, Nantong, China.
Cheng SunJiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. suncheng1975@ntu.edu.cn.
Lihua ShenDepartment of Neurology, Affiliated Hospital of Nantong University, Nantong, China. lihuashennt@126.com.

Funding

National Natural Science Foundation of China 32271193the Foundation of Jiangsu Province Research Hospital YJXYY202204-YSC10the Research Project of Jiangsu Provincial Health Commission ZD2022040
6 · The paper itself

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder, and its pathogenesis is closely associated with oxidative stress, mitochondrial dysfunction, and iron-dependent cell death. In our previous study, we showed that 3-n-butylphthalide (NBP) alleviates behavioral deficits in a PD mouse model. However, the underlying mechanisms remain unclear. Here, we found that NBP treatment significantly attenuated ferroptosis induced by Erastin or RSL3 in SH-SY5Y cells, as evidenced by improved cell viability, reduced reactive oxygen species (ROS) production, decreased mitochondrial oxidative stress, and lower levels of lipid peroxidation. Molecular docking analysis revealed that NBP interacts with ACSL4 at residues PRO-404, TYR-425, VAL-447, ILE-526, and LYS-649. A cellular thermal shift assay combined with site-directed mutagenesis indicated that PRO-404 and ILE-526 are critical for the interaction between ACSL4 and NBP. Furthermore, pulse-chase experiments showed that NBP enhances ACSL4 protein stability. Notably, ACSL4 overexpression abrogated the protective effects of NBP in Erastin- or RSL3-treated cells. Collectively, our data indicate that NBP protects SH-SY5Y cells from ferroptosis, likely through the suppression of ACSL4-mediated lipid peroxidation. These results highlight the therapeutic potential of NBP for treating ferroptosis-related neurodegenerative diseases such as PD.

Indexed as

BenzofuransCoenzyme A LigasesFerroptosisLipid PeroxidationNeuroprotective AgentsCarbolinesCell Line, TumorCell SurvivalHumansLong-Chain-Fatty-Acid-CoA LigaseMitochondriaMolecular Docking SimulationOxidative StressPiperazinesReactive Oxygen Species3-n-butylphthalideBenzofuransCarbolinesCoenzyme A LigaseserastinLong-Chain-Fatty-Acid-CoA LigaseNeuroprotective AgentsPiperazinesReactive Oxygen SpeciesRSL3 compound3-n-ButylphthalideACSL4FerroptosisLipid peroxidationSH-SY5Y cells

Identifiers

PMID41545774

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.