天然中草药单体成分灯盏花素减轻缺血性脑卒中的潜在作用

吴建宇1 柴雪洁2 于媛媛3 杨林风4*

doi:10.16098/j.issn.0529-1356.2025.06.005

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解剖学报 ›› 2025, Vol. 56 ›› Issue (6) : 659-672. DOI: 10.16098/j.issn.0529-1356.2025.06.005

神经生物学

天然中草药单体成分灯盏花素减轻缺血性脑卒中的潜在作用

吴建宇¹ 柴雪洁² 于媛媛³杨林风^4*

作者信息 +

Potential role of natural herbal monomer scutellarein in alleviating ischemic stroke

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

Author information +

文章历史 +

摘要

目的通过网络药理学以体内实验验证探讨天然中草药单体成分灯盏花素在缓解缺血性脑卒中（IS）中的潜在作用。方法通过SwissTargetPrediction和PharmMapper数据库筛选灯盏花素(Scu)作用靶标，并通过UniProt对靶标名称进行标准化。以“缺血性脑卒中”为关键词，从GEO数据库中检索GSE22255数据集，使用R语言进行标准化处理，利用 | log10FC | ≥ 1和P<0.05为条件筛选差异基因。Venny 2.1.0图构建获取两者交集作用靶标。利用STRING和Cytoscape软件构建蛋白-蛋白相互作用（PPI）网络，并进行基因本体论（GO）功能分析和京都基因与基因组百科全书（KEGG）通路富集分析；AutoDock Vina 1.5.6对灯盏花素与核心靶标进行分子对接，并进行结果可视化。通过构建大脑中动脉闭塞（MCAO）小鼠模型，分为假手术组、MCAO组、MCAO+灯盏花素干预组（MCAO+Scu），Real-time PCR检测小鼠缺血皮质区核心靶标及通路相关蛋白mRNA表达变化。结果共获取325个灯盏花素潜在靶标，2168个IS相关差异靶标。Venny图获取29个两者交集作用靶标。GO功能分析得到51条生物学过程（BP），5条细胞组分（CC）及8条分子功能（MF）条目；KEGG通路富集分析突出PI3K/Akt代谢等通路。PPI可视化网络根据度值筛选识别出Caspase-3（CASP3）、表皮生长因子受体（EGFR）、前列腺素内过氧化物合酶2（PTGS2）、过氧化物酶体增殖物激活受体α（PPARA）和白细胞介素2（IL-2）作为关键枢纽蛋白；分子对接显示，灯盏花素与枢纽蛋白具有较强的结合能力。Real-time PCR实验结果表明，灯盏花素对核心靶标及通路相关蛋白mRNA表达具有调控作用。结论灯盏花素在MCAO小鼠模型中可通过调控CASP3、EGFR、PTGS2、PPARA及IL-2等靶点，激活PI3K/Akt通路，发挥神经保护作用，具有多靶点、多通路等特点。

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.

导出引用

吴建宇柴雪洁于媛媛杨林风. 天然中草药单体成分灯盏花素减轻缺血性脑卒中的潜在作用[J]. 解剖学报. 2025, 56(6): 659-672 https://doi.org/10.16098/j.issn.0529-1356.2025.06.005

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

中图分类号： R328 R743.3

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