Dl-3-n-Butylphthalide alleviates cerebral ischemia-reperfusion injury via the miR-20a-5p/XIAP axis

  • Neurol Res. 2025 Jul 25:1-16. doi: 10.1080/01616412.2025.2539488.
Guang Yao  1 ,  Juan Xu  2 ,  Qiong Chen  1 ,  Ruping Xiang  1
Affiliations
  • 1. Department of Neurology, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan, China.
  • 2. Department of Rehabilitation Therapy, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan, China.
PMID: 40888394 DOI: 10.1080/01616412.2025.2539488
Abstract

Objective: This study aims to explore the neuroprotective effects of Dl-3-n-Butylphthalide (NBP) against cerebral ischemia-reperfusion injury (CIRI), with a focus on NBP's underlying molecular mechanism.

Methods: A CIRI rat model was established, followed by treatment with NBP with/without microRNA-20a-5p (miR-20a-5p) mimic or negative control. Neurological deficits, brain infarct size, and histopathological changes were assessed. In vitro, an oxygen-glucose deprivation/reoxygenation (OGD/R)-induced PC12 cell model was developed, followed by cell viability and Apoptosis evaluation. miR-20a-5p, X-linked inhibitor of Apoptosis protein (XIAP), and apoptosis-related protein levels were detected. A dual-luciferase reporter assay was performed to confirm the interaction between miR-20a-5p and XIAP.

Results: NBP treatment significantly restored neurological function, reduced infarct size, and inhibited neuronal Apoptosis. Mechanistically, NBP downregulated miR-20a-5p and upregulated XIAP. The protective effects of NBP were abolished by miR-20a-5p overexpression.

Conclusion: NBP exerts neuroprotective effects against CIRI by modulating the miR-20a-5p/XIAP axis. NBP may serve as a therapeutic agent for CIRI.

Keywords
Dl-3-n-Butylphthalide; X-linked inhibitor of apoptosis protein; cerebral infarction; cerebral ischemia-reperfusion; microRNA-20a-5p.
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