Molecular_Docking.

ObjectiveTo investigate the pharmacodynamic material basis, multi-target mechanisms of Chelidonii Herba in treating chronic obstructive pulmonary disease (COPD), and its hepatotoxicity pathways using network pharmacology, network toxicology, and molecular docking.MethodsActive components and targets of Chelidonii Herba were screened via Traditional Chinese Medicine Systems Pharmacology (TCMSP), SwissTargetPrediction (STP), and PharmMapper databases. COPD and hepatotoxicity targets were obtained from GeneCards and OMIM. Venn diagrams identified shared targets. Protein-protein interaction (PPI) networks were constructed using STRING, with core targets filtered via CytoNCA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in Metascape. Molecular docking was validated by AutoDock Vina, and immune infiltration was analyzed using the GSE55962 dataset.ResultsTwenty active components and 108 potential targets of Chelidonii Herba were identified. Eighty shared targets intersected with COPD, and 96 with hepatotoxicity. Seven core targets for COPD treatment (CASP3, PPARG, PTGS2, CDK2, ALB, HSP90AA1, ESR1) and hepatotoxicity (PPARG, ESR1, CASP3, PTGS2, ESR2, CALM3, ALB) were determined. KEGG enrichment revealed COPD mechanisms involving PI3K-Akt, VEGF, and cGMP-PKG pathways, while hepatotoxicity implicated VEGF, PI3K-Akt, and estrogen signaling. Core components (e.g., dihydrochelerythrine, oxysanguinarine) exhibited strong binding to targets (binding energy ≤ −5.0 kcal/mol, partial ≤ −7.0 kcal/mol). Immune infiltration analysis linked core targets to macrophages M2 and γδ T cells.ConclusionChelidonii Herba treats COPD primarily through alkaloids modulating shared targets (CASP3, PPARG, PTGS2) via PI3K-Akt pathways, while concurrently inducing hepatotoxicity through VEGF and estrogen signaling. This dual efficacy-toxicity profile necessitates cautious clinical application and experimental validation to define safe therapeutic windows.

目的 采用网络药理学、网络毒理学与分子对接技术，探究白屈菜（Chelidonii Herba）治疗慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）的药效物质基础、多靶点作用机制及其肝毒性通路。
方法 依托中药系统药理学数据库（Traditional Chinese Medicine Systems Pharmacology, TCMSP）、SwissTargetPrediction（STP）及PharmMapper数据库，筛选白屈菜的活性成分与作用靶点；从GeneCards与OMIM数据库获取COPD及肝毒性相关靶点；通过韦恩图筛选二者的交集靶点；利用STRING数据库构建蛋白质相互作用（protein-protein interaction, PPI）网络，并通过CytoNCA插件筛选核心靶点；借助Metascape平台开展基因本体（Gene Ontology, GO）及京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析；采用AutoDock Vina软件完成分子对接验证，并利用GSE55962数据集开展免疫浸润分析。
结果 共筛选得到白屈菜的20种活性成分与108个潜在作用靶点；与COPD靶点交集得到80个共同靶点，与肝毒性靶点交集得到96个共同靶点；分别确定治疗COPD的7个核心靶点（CASP3、PPARG、PTGS2、CDK2、ALB、HSP90AA1、ESR1）及介导肝毒性的7个核心靶点（PPARG、ESR1、CASP3、PTGS2、ESR2、CALM3、ALB）；KEGG富集分析显示，白屈菜治疗COPD的潜在通路涉及PI3K-Akt、VEGF及cGMP-PKG信号通路，而其介导肝毒性的通路则涉及VEGF、PI3K-Akt及雌激素信号通路；核心活性成分（如二氢白屈菜红碱（dihydrochelerythrine）、氧化血根碱（oxysanguinarine））与靶点结合活性较强，结合能≤-5.0 kcal/mol，部分成分结合能≤-7.0 kcal/mol；免疫浸润分析结果显示，核心靶点与M2型巨噬细胞及γδ T细胞存在显著关联。
结论 白屈菜主要通过生物碱类成分调控CASP3、PPARG、PTGS2等共同靶点，经PI3K-Akt信号通路发挥治疗COPD的作用，同时可通过VEGF及雌激素信号通路诱导肝毒性。该研究揭示的双效-毒特性提示临床应用需谨慎，并需开展进一步实验验证以明确其安全治疗窗口。