Potential role of natural herbal monomer scutellarein in alleviating ischemic stroke

WU Jian-yu1  CHAI Xue-jie2  YU Yuan-yuan3  YANG Lin-feng4*

doi:10.16098/j.issn.0529-1356.2025.06.005

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Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (6) : 659-672. DOI: 10.16098/j.issn.0529-1356.2025.06.005

Neurbiology

Potential role of natural herbal monomer scutellarein in alleviating ischemic stroke

WU Jian-yu¹ CHAI Xue-jie² YU Yuan-yuan³ YANG Lin-feng^4*

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Abstract

Objective To investigate the potential mechanisms by which the natural herbal monomer scutellarin alleviates ischemic stroke (IS) using network pharmacology and in vivo experimental validation. Methods Potential targets of scutellarin were predicted using SwissTargetPrediction and PharmMapper, and standardized via UniProt. IS-related differentially expressed genes (DEGs) were obtained from the GSE22255 dataset in the GEO database, with screening criteria of | log10 FC | ≥1 and P<0.05. Venny 2.1.0 analysis was used to identify overlapping targets. Protein-protein interaction (PPI) networks were constructed using STRING and visualized in cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Molecular docking was conducted using AutoDock Vina 1.5.6 to assess the binding affinity between scutellarin and hub targets. Middle cerebral artery occlusion (MCAO) mouse model was established and divided into sham, MCAO, and MCAO + scutellarin groups. Real-time PCR was used to detect mRNA expression of hub genes and phosphatidylinositol 3-kinase(PI3K)/Akt pathway components in the ischemic cortex. Results A total of 325 scutellarin targets and 2168 IS-related DEGs were identified, with 29 overlapping targets. GO analysis yielded 51 biological processes, 5 cellular components, and 8 molecular functions. KEGG enrichment highlighted PI3K/Akt and metabolic pathways. PPI analysis identified Caspase-3, epidermal growth factor receptor (EGFR), prostaglandin-endoperoxide synthase 2 (PTGS2), peroxisome proliferator activated receptor alpha (PPARA), and interleukin-2 (IL-2) as key hub proteins. Molecular docking showed strong binding affinities between scutellarin and these proteins. Real-time PCR result confirmed that scutellarin modulated the expression of hub genes and activated the PI3K/Akt pathway. Conclusion In the MCAO mouse model, scutellarin exerts neuroprotective effects by modulating targets such as CASP3, EGFR, PTGS2, PPARA, and IL-2, and activating the PI3K/Akt signaling pathway, exhibiting multi-target and multi-pathway characteristics.

Key words

Network pharmacology / Ischemic stroke / Scutellarin / Molecular docking / Real-time PCR / Mouse

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WU Jian-yu CHAI Xue-jie YU Yuan-yuan YANG Lin-feng. Potential role of natural herbal monomer scutellarein in alleviating ischemic stroke[J]. Acta Anatomica Sinica. 2025, 56(6): 659-672 https://doi.org/10.16098/j.issn.0529-1356.2025.06.005

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