基于网络药理学与分子对接探讨越婢加半夏汤治疗慢性阻塞性肺疾病的作用机制

Mechanisms of Yuebi plus Banxia Decoction in Treating Chronic Obstructive Pulmonary Disease: A Study Based on Network Pharmacology and Molecular Docking

摘要: 目的：探讨越婢加半夏汤治疗慢性阻塞性肺疾病的作用机制。方法：通过TCMSP平台检索获取越婢加半夏汤活性成分及靶基因，运用Swiss Target Prediction数据库预测潜在靶基因，使用GeneCards数据库筛选慢性阻塞性肺疾病相关靶基因，通过Venny 2.1获取越婢加半夏汤与慢性阻塞性肺疾病的共同靶基因。交集靶基因运用String数据库构建蛋白质互作(PPI)网络，采用Cytoscape软件构建“中药–有效成分–靶点”网络。运用DAVID数据库进行GO和KEGG富集分析，使用Autodock Tools对潜在有效成分与关键靶基因进行分子对接验证。结果：共筛选出越婢加半夏汤145个活性成分及959个药物作用靶基因，获得2419个COPD相关靶基因，449个交集靶基因。核心靶基因GO功能富集条目277个，KEGG通路127条。越婢加半夏汤的主要活性成分包括Glyuranolide、Glabridin、Glyasperin B、Pectolinarigenin、Glypallichalcone等，它们可能通过作用于TP53、SRC、STAT3、PIK3R1、PIK3CA、GRB2、PIK3CD、EP300、ESR1、EGFR、JAK2、PTPN11、PLCG1、JUN、PTK2、CREBBP、RELA、KDR、JAK3等靶点，可能通过调控癌症发展、PI3K-Akt信号通路、AGE-RAGE信号通路参与糖尿病并发症、前列腺癌、脂质和动脉粥样硬化、卡波西肉瘤相关疱疹病毒感染、EGFR酪氨酸激酶抑制剂抵抗，胰腺癌、癌症中枢碳代谢、乙型肝炎等途径。结论：越婢加半夏汤通过多成分–多靶点–多通路协同作用治疗COPD，为越婢加半夏汤治疗COPD作用机制和临床应用提供理论依据。

Abstract: Objective: To investigate the mechanism of the treatment of chronic obstructive pulmonary disease (COPD) with Yuebi decoction plus Banxia. Methods: Active components and Target genes of Yuebi decoction plus Banxia were retrieved by TCMSP platform, potential target genes were predicted by Swiss Target Prediction database, chronic obstructive pulmonary disease related target genes were screened by GeneCards database, and Venny was used 2.1 To obtain the common target gene of Yuebi decoction plus Banxia and chronic obstructive pulmonary disease. The protein interaction (PPI) network was constructed by using String database and Cytoscape software. The “Chinese Materia Medica—Active Ingredients—target” network was constructed. DAVID database was used for GO and KEGG enrichment analysis, and Autodock Tools was used to verify the molecular docking between potential active components and key target genes. Results: A total of 145 active ingredients and 959 drug action target genes were screened out, 2419 COPD related target genes and 449 intersection target genes were obtained. There were 277 GO functional enrichment items and 127 KEGG pathways of core target genes. The main active components of the decoction include Glyuranolide, Glabridin, Glyasperin B. Pectolinarigenin, Glypallichalcone, etc., which may be induced by the action of TP53, SRC, STAT3, PIK3R1, PIK3CA, GRB2, PIK3CD, EP300, ESR1, EGFR, JAK2, PTPN11, PLCG1, JUN, PTK2, CREBBP, RELA, KDR, JAK3 and potentially through Pathways in cancer, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Prostate cancer, Lipid and atherosclerosis, Kaposi sarcoma-associated herpesvirus infection, EGFR tyrosine kinase inhibitor resistance, Pancreatic cancer, Centrral carbon metabolism in cancer, Hepatitis B, etc. Conclusion: Yuebi Decoction plus Banxia exhibits multi-component, multi-target, and multi-pathway characteristics in treating COPD. These findings provide a theoretical basis for understanding the mechanism and clinical application of Yuebi Decoction plus Banxia in treating COPD.