中西医结合慢性病杂志

目的 运用中药网络药理学方法结合分子对接技术，初步探究甘草泻心汤治疗化疗后恶心呕吐（chemotherapy-induced nausea and vomiting,CINV）的作用机制。方法 从中药系统药理学数据库和分析平台获取甘草泻心汤的活性化合物及其作用靶点；使用Perl软件通过UniProt数据库匹配靶点对应的标准基因符号；从GeneCards、OMIM、PharmGKB、Therapeutic Target Database和DrugBank 5个数据库中检索CINV相关疾病靶点基因；利用R软件筛选甘草泻心汤靶点与CINV靶点的交集基因；通过Cytoscape 3.10.3软件绘制“药物-成分-靶点-疾病”交互网络图；基于STRING平台构建蛋白质-蛋白质相互作用网络；对关键活性成分与核心靶点进行分子对接，验证其结合活性；采用R 4.2.2软件进行基因本体（gene ontology,GO）功能富集分析和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析。结果 基于口服生物利用度（oral bioavailability,OB）和类药性（drug-likeness,DL）阈值筛选，获得甘草泻心汤118种去重活性成分，甘草泻心汤与CINV存在31个共同作用靶点。GO富集分析共获得1831条显著条目，包括生物过程1621条、细胞组分79条和分子功能131条；KEGG通路分析筛选出128条相关通路。甘草泻心汤的主要活性成分为槲皮素、β-谷甾醇、汉黄芩素、山柰酚、荷叶碱；核心靶点为蛋白激酶B、白细胞介素-1β、细胞间黏附分子-1、肿瘤蛋白p53、表皮生长因子受体、前列腺素内过氧化物合酶2、B细胞淋巴瘤-2、雌激素受体α、连环蛋白β1。分子对接表明，活性成分（如槲皮素）与核心靶点前列腺素内过氧化物合酶2结合稳定，作用机制涉及外源性刺激响应、胶质细胞增殖、细胞凋亡等生物过程，并通过调控磷脂酰肌醇3激酶-蛋白激酶B、缺氧诱导因子-1、Janus激酶-信号转导子和转录激活子等信号通路发挥抗CINV作用。结论 甘草泻心汤通过槲皮素、β-谷甾醇、汉黄芩素等活性成分，作用于蛋白激酶B、前列腺素内过氧化物合酶2等多靶点，调控炎症反应、细胞凋亡及相关信号通路，从而发挥治疗化疗后恶心呕吐的作用。

Objective To explore the mechanism of Gancao Xiexin Tang in treating chemotherapy-induced nausea and vomiting(CINV) using traditional Chinese medicine network pharmacology methods combined with molecular docking technology. Methods The active compounds and their targets of Gancao Xiexin Tang were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform TCMSP. Perl software was used to match the standard gene symbols corresponding to the targets in the UniProt database. CINV related disease target genes were retrieved from five databases: GeneCards, OMIM, PharmGKB, Therapeutic Target Database, and DrugBank. Using R software to screen the intersection genes between the targets of Gancao Xiexin Tang and CINV, a "drug ingredient target disease" interaction network diagram was drawn using Cytoscape 3.10.3 software. A protein-protein interaction network was constructed based on the STRING platform to perform molecular docking between key active ingredients and core targets to verify their binding activity. Gene ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed using R 4.2.2 software. Results Based on oral bioavailability(OB) and drug likeness(DL) threshold screening, 118 de duplicated active ingredients were obtained from Gancao Xiexin Tang. Gancao Xiexin Tang has 31 common targets with CINV. GO enrichment analysis showed a total of 1831 significant entries, including 1621 for biological processes, 79 for cellular components, and 131 for molecular functions; KEGG pathway analysis identified 128 relevant pathways. The main active ingredients of Gancao Xiexin Tang are quercetin, β-sitosterol, baicalein, kaempferol, and hesperetin; The core targets are AKT1, IL-1 β, ICAM1, TP53, EGFR, PTGS2, BCL2, ESR1, and CTNNB1. Molecular docking showed that the active ingredient(such as quercetin) binds stably to the core target PTGS2, and its mechanism of action involves biological processes such as exogenous stimulus response, glial cell proliferation, and apoptosis. It exerts anti CINV effects by regulating signaling pathways such as PI3K-Akt, HIF-1, JAK-STAT, etc. Conclusion Gancao Xiexin Tang acts on multiple targets such as Akt1 and PTGS2 through active ingredients such as quercetin, β-sitosterol, and baicalein, regulating inflammatory response, cell apoptosis, and related signaling pathways, thereby treating nausea and vomiting after chemotherapy.