基于网络药理学和分子对接探讨四物汤治疗肝纤维化及肝硬化的潜在机制

Exploring the Mechanism of Siwu Decoction in Treating Liver Fibrosis and Liver Cirrhosis Based on Network Pharmacology and Molecular Docking

摘要: 目的：本文借助网络药理学和分子对接技术探讨四物汤治疗肝纤维化与肝硬化的相关作用靶点和作用机制。方法：通过TCMSP数据库筛选四物汤组成药材(熟地黄、当归、白芍、川芎)的活性成分，采用Uniprot数据库校准。在GeneCards数据库、OMIM数据库和TTD数据库筛选肝纤维化和肝硬化相关靶点，并构建中药成分与疾病交集靶点，利用Cytoscape软件和微生信平台进行可视化分析。将交集靶点导入STRING数据库构建蛋白质相互作用(PPI)网络，采用CytoNCA插件筛选核心靶点。通过Metascape数据库进行富集分析，利用分子对接进行验证。结果：共筛选出四物汤活性成分20个及相关靶点109个，肝纤维化与肝硬化交互靶点基因1434个，中药与疾病的交互靶点基因54个，6个核心靶点分别为AKT1、IL6、RELA、JUN、TNF、BCL2。在GO功能富集分析中得到985条条目；KEGG通路富集分析揭示162条相关信号通路。分子对接结果中，36组分子对接的结合能有33组低于−5 kcal/mol，结合活性良好。结论：本研究证实，四物汤可通过多成分、多靶点、多通路干预肝纤维化及肝硬化的进程，这一发现为其后续的新药开发与临床推广应用奠定了坚实的理论基础。

Abstract: Objective: This study utilized network pharmacology and molecular docking technology to explore the relevant targets and mechanisms of Siwu Decoction in the treatment of hepatic fibrosis and cirrhosis. Methods: Active ingredients of the constituent herbs of Siwu Decoction (Rehmanniae Radix Praeparata, Angelicae Sinensis Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma) were screened using the TCMSP database and standardized via the Uniprot database. Disease-related targets for hepatic fibrosis and cirrhosis were retrieved from the GeneCards, OMIM, and TTD databases. Intersecting targets between the herbal components and the disease were identified and visualized using Cytoscape software and the micro-bioinformatics platform. The protein-protein interaction (PPI) network of the intersecting targets was constructed using the STRING database, and core targets were identified using the CytoNCA plugin. Enrichment analysis was performed using the Metascape database and validation was performed using molecular docking. Results: A total of 20 active ingredients and 109 related targets of Siwu Decoction were screened. There were 1434 intersecting target genes related to hepatic fibrosis and cirrhosis, and 54 intersecting target genes between the herbal medicine and the disease. The six core targets identified were AKT1, IL6, RELA, JUN, TNF, and BCL2. GO functional enrichment analysis yielded 985 entries, and KEGG pathway enrichment analysis revealed 162 related signaling pathways. Among the molecular docking results, the binding energy in 33 out of 36 molecular docking groups was lower than −5 kcal/mol, indicating favorable binding activity. Conclusion: This study confirms that Siwu Decoction can intervene in the progression of hepatic fibrosis and cirrhosis through multiple components, targets, and pathways. This finding lays a solid theoretical foundation for subsequent new drug development and clinical promotion and application.