基于网络药理学与分子对接分析探讨半夏泻心汤防治幽门螺杆菌感染的作用机制

Exploring the Mechanism of Action of Banxia Xiexin Decoction in Preventing and Treating Helicobacter pylori Infection Based on Network Pharmacology and Molecular Docking Analysis

摘要: 研究目的：以网络药理学和分子对接技术为基础，探讨半夏泻心汤的主要活性化合物、潜在靶点及相关的通路，以根除幽门螺杆菌(Hp)的感染。研究方法：该研究以中药系统药理资料库(TCMSP)、SwissADME、SwissTargetPrediction资料库为基础，对半夏泻心汤的活性成分及其对应靶点进行筛选；同时，幽门螺杆菌感染相关疾病靶点的获取是通过GeneCards和OMIM数据库获得的。借助于String数据库构建蛋白互作(PPI)网络，利用Cytoscape3.8.0构建“药物–成分–靶点”网络，然后对其中的主要活性成分及核心靶标进行识别。进一步采用R 4.4.3对关键靶点进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析，以揭示其潜在生物学过程与信号通路。最后，最后，利用CB-Dock2进行分子对接，以验证活性成分与核心靶点之间的结合能力。研究结果：本次研究共筛选出160种活性成分，被认定为关键有效化合物的有栎皮素、含黄芩素和山酚，它们对应的靶点有1127个。与2566个Hp感染相关靶点进行交集分析后，得到458个共同作用靶点，包括STAT3、MAPK1、AKT1和TP53等。蛋白互作网络分析进一步识别出STAT3、MAPK1、AKT1和ESR1处于网络核心位置。富集分析结果显示，这些靶点显著富集于PI3K-Akt、MAPK、FoxO等96条信号通路，提示半夏泻心汤可能通过多通路协同发挥治疗效应。分子对接结果表明，槲皮素、山柰酚等类黄酮成分与AKT1、ESR1等靶标均表现出较强的结合活性，且结合能量均低于–7.0 kcal/mol，证实了其良好的结合稳定性。研究结论：半夏泻心汤通过其多组分特性，借助多靶点作用与多通路调控的协同机制，实现对Hp毒力活性的抑制、炎症信号的调节、黏膜屏障功能的恢复以及炎癌转化过程的干预，从而达成抗Hp效应。

Abstract: Objective: This paper aims to explore the main active compounds, potential targets, and related pathways of Banxia Xiexin Decoction in eradicating Helicobacter pylori (Hp) infection based on network pharmacology and molecular docking technology. Methods: The active ingredients and their targets in Banxia Xiexin Decoction were identified using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), the SwissADME database, and the SwissTargetPrediction database. Hp infection-related targets were retrieved from the GeneCards and OMIM databases. Cytoscape 3.8.0 and the String database were utilized to create the “drug-compound-potentialtarget” network for the Chinese herbal compound and the protein-protein interaction (PPI) network diagram, respectively, in order to analyze the primary active ingredients and target proteins present in the decoction. R version 4.4.3 was used to conduct functional enrichment analysis for Gene Ontology (GO) and pathway enrichment analysis for Kyoto Encyclopedia of Genes and Genomes (KEGG). CB-Dock2 was utilized to perform molecular docking, which allowed the binding between the main parts and the targets to be confirmed. Results: A total of 160 active ingredients were screened out, among which the main effective components included quercetin, wogonin, and kaempferol, corresponding to 1127 drug targets. By intersecting with 2566 Hp infection-related targets, 458 core targets were obtained, mainly including STAT3, MAPK1, AKT1, and TP53. The main targets were STAT3, MAPK1, AKT1, and ESR1, according to the PPI network. Enrichment analysis indicated that Banxia Xiexin Decoction regulates 96 signaling pathways, such as PI3K-Akt, MAPK, and FoxO. Molecular docking verification revealed that the binding energy of quercetin, kaempferol, etc., with targets such as AKT1 and ESR1 was lower than −7.0 kcal/mol, indicating stable binding. Conclusion: Banxia Xiexin Decoction demonstrates anti-Hp effects through synergistic actions involving multiple components, targets, and pathways. These effects include the inhibition of virulence factor activity, modulation of inflammatory signals, repair of the mucosal barrier, and suppression of inflammation-related cancer transformation.