基于网络药理学及分子对接技术探析四白溃愈汤治疗胃溃疡机制

Exploring the Mechanism of Sibai Kuiyu Decoction in Treating Gastric Ulcer Based on Network Pharmacology and Molecular Docking Technology

摘要: 目的：运用网络药理学研究四白溃愈汤治疗胃溃疡作用机制，通过分子对接技术进行验证。方法：检索TCMSP获得四白溃愈汤的活性成分及作用靶点，检索GeneCards、OMIM获得胃溃疡相关靶点，获取四白溃愈汤–胃溃疡的交集靶点；运用Cytoscape软件构建可视化网络，进行蛋白相互作用、基因本体功能及京都基因与基因组百科全书通路富集分析，最后对网络药理学预测的结果进行分子对接验证。结果：筛选得到四白溃愈汤中的活性成分67个，与胃溃疡交集的靶点444个；GO功能富集分析表明，四白溃愈汤治疗胃溃疡涉及多个生物学过程，主要集中于信号传导、细胞增殖的正调控、磷酸化、凋亡的负调控、炎症反应等方面。KEGG富集分析发现，四白溃愈汤可能干预IL-17信号通路、PI3K-Akt信号通路、HIF-1信号通路、肿瘤坏死因子信号通路、Toll样受体信号通路的表达，发挥治疗胃溃疡的作用。通过分子对接技术，发现四白溃愈汤含有的槲皮素、β-谷甾醇、山柰酚、瓜叶菊酯1、8-甲氧基山奈酚等活性成分与AKT1、HSP90AA1、SRC、ESR1等关键靶点的结合性较好。结论：四白溃愈汤富含槲皮素、β-谷甾醇、山柰酚、瓜叶菊酯1、8-甲氧基山奈酚等活性成分，通过作用于AKT1、HSP90AA1、SRC、ESR1等关键靶点，调控IL-17信号通路、PI3K-Akt信号通路、HIF-1信号通路及肿瘤坏死因子信号通路，发挥抗炎、抗氧化、抗凋亡等治疗效应，促进胃黏膜溃疡的愈合。

Abstract: Objective: The mechanism of action of Sibai Kuiyu Decoction in treating gastric ulcer was studied through network pharmacology and verified using molecular docking technology. Methods: The active components and targets of Sibai Kuiyu Decoction were retrieved from TCMSP, and gastric ulcer-related targets were obtained from GeneCards and OMIM to identify the intersection targets between Sibai Kuiyu Decoction and gastric ulcer. Cytoscape software was used to construct a visual network for protein-protein interaction, gene ontology function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the results predicted by network pharmacology were verified through molecular docking. Results: Sixty-seven active ingredients were identified in Sibai Kuiyu Decoction, and 444 targets intersecting with gastric ulcer were found. GO functional enrichment analysis indicated that the treatment of gastric ulcer with Sibai Kuiyu Decoction involves multiple biological processes, mainly focusing on signal transduction, positive regulation of cell proliferation, phosphorylation, negative regulation of apoptosis, and inflammatory response. KEGG enrichment analysis revealed that Sibai Kuiyu Decoction may intervene in the expression of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, tumor necrosis factor signaling pathway, and Toll-like receptor signaling pathway to exert its therapeutic effect on gastric ulcer. Through molecular docking technology, it was discovered that the active ingredients contained in Sibai Kuiyu Decoction, such as quercetin, β-sitosterol, kaempferol, and 8-methoxykaempferol, exhibit good binding affinity with key targets including AKT1, HSP90AA1, SRC, and ESR1. Conclusion: Sibai Kuiyu Decoction is rich in active ingredients such as quercetin, β-sitosterol, kaempferol, hedyotis diffusa ester 1, and 8-methoxykaempferol. By acting on key targets such as AKT1, HSP90AA1, SRC, ESR1, etc., it regulates the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and tumor necrosis factor signaling pathway, exerting anti-inflammatory, antioxidant, anti-apoptotic, and other therapeutic effects to promote the healing of gastric mucosal ulcers.