基于网络药理学和分子对接技术探讨四逆四苓汤“异病同治”PID、EP及子宫颈HPV感染的作用机制

Exploring the Mechanism of “Treating Different Diseases with the Same Treatment Principle” of Sini and Siling Decoction in PID, EP, and Cervical HPV Infection Based on Network Pharmacology and Molecular Docking Techniques

摘要: 目的：基于网络药理学和分子对接技术，探讨四逆四苓汤治疗女性盆腔炎性疾病(PID)、子宫内膜息肉(EP)及子宫颈人乳头瘤病毒(HPV)感染的“异病同治”潜在药理学作用机制。方法：使用中药系统药理学数据库与分析平台(TCMSP)结合文献获取四逆四苓汤的化学成分及其作用靶点，通过人类孟德尔遗传综合数据库(OMIM)、GeneCards、DisGeNET数据库挖掘PID、EP及子宫颈HPV感染的疾病靶点，取交集后得到共有靶点。利用Cytoscape 3.9.1软件并构建“中药有效成分–靶点–疾病”多重网络。采用微生信平台进行基因本体论功能富集(GO)与基因百科全书(KEGG)富集分析。最后使用AutoDock软件、PyMOL软件对关键交集靶点与主要活性成分进行分子对接和可视化展示。结果：从四逆四苓汤中共筛选出170个活性成分，槲皮素、山奈酚、异鼠李素等为其核心成分。确定127个疾病共同靶点，其中degree值排名前10的靶点包括环氧化酶-2 (PTGS2)、雌激素受体1 (ESR1)、雌激素受体2 (ESR2)、环氧化酶-1 (PTGS1)等。GO分析结果表明：四逆四苓汤治疗三者疾病主要涉及基因表达的正调控等生物过程。KEGG分析表明: 四逆四苓汤通过调节白介素-17 (IL-17)信号通路、肿瘤坏死因子(TNF)信号通路等发挥对以上三种疾病的“异病同治”作用。分子对接结果显示：PTGS2与β谷甾醇的结合活性最强，为−49.45 kJ/mol。结论：四逆四苓汤可以通过调控炎症反应、性激素和免疫功能发挥对PID、EP及子宫颈HPV感染的“异病同治”作用。

Abstract: Objective: Based on network pharmacology and molecular docking technology, to explore the potential pharmacological mechanism of “treating different diseases with the same treatment principle” of Sini and Siling Decoction in treating pelvic inflammatory disease (PID), endometrial polyp (EP), and cervical human papilloma virus (HPV) infection in women. Methods: The chemical components and target proteins of Sini and Siling Decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and literature review. Disease targets for PID, EP, and cervical HPV infection were collected from OMIM, GeneCards, and DisGeNET databases. Common targets were identified through intersection analysis. Cytoscape 3.9.1 software was used to build a “herb-active component-target-disease” network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the Microbioinformatics platform. Molecular docking and visualization of key targets with main active components were conducted using AutoDock and PyMOL software. Results: 170 active components were identified from Sini and Siling Decoction, with quercetin, kaempferol, and isorhamnetin as core components. 127 common disease targets were identified, including prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and prostaglandin-endoperoxide synthase 1 (PTGS1) as top 10 targets by degree value. GO analysis showed the treatment mainly involved biological processes like positive regulation of gene expression. KEGG analysis revealed its effects through regulating interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways. Molecular docking showed the strongest binding activity between PTGS2 and β-sitosterol (−49.45 kJ/mol). Conclusion: Sini and Siling Decoction may achieve “treating different diseases with the same treatment principle” for PID, EP, and cervical HPV infection by regulating inflammatory responses, sex hormones, and immune functions.