基于网络药理学与分子对接技术分析和胃化湿汤治疗胃黏膜肠上皮化生的作用机制

Analysis of the Mechanism of Hewei Huashi Decoction in the Treatment of Gastric Intestinal Metaplasia Based on Network Pharmacology and Molecular Docking Technology

摘要:

目的：基于网络药理学与分子对接技术分析和胃化湿汤治疗胃黏膜肠上皮化生（IM） 的潜在作用机制。方法：利用TCMSP、HERB数据库筛选和胃化湿汤的活性成分及作用靶点；通过GeneCards、OMIM疾病数据库获取胃黏膜IM相关靶点；取交集后获得潜在治疗靶点。利用STRING数据库构建蛋白互作（PPI） 网络，并利用Cytoscape软件筛选核心靶点。通过Metascape数据库进行基因本体（GO） 功能与京都基因与基因组百科全书（KEGG） 通路富集分析。并利用PyMOL、AutoDock等分子对接软件验证关键活性成分与核心靶点的结合能力。结果：共筛选到和胃化湿汤活性成分130个，对应靶点488个，胃黏膜IM疾病靶点1 987个，潜在作用靶点186 个。筛选得到槲皮素、β-谷甾醇、柚皮素、木犀草素等关键活性成分， 以及肿瘤蛋白P53 （TP53）、蛋白激酶B1 （AKT1）、白细胞介素-6 （IL-6）、肿瘤坏死因子（TNF）、表皮生长因子受体（EGFR） 等核心靶点。富集分析表明，潜在治疗靶点显著富集于磷脂酰肌醇3-激酶（PI3K） -Akt信号通路、癌症通路、糖尿病并发症中的晚期糖基化终末产物-受体（AGE-RAGE） 信号通路等，涉及细胞增殖、凋亡、炎症反应等生物学过程。分子对接结果显示，关键活性成分与核心靶点的分子对接结合能均在-8.16～-4.97 kcal/mol之间。结论：和胃化湿汤通过槲皮素、β-谷甾醇、柚皮素、木犀草素等关键活性成分，协同作用于TP53、AKT1、IL-6、TNF、EGFR等核心靶点，调控PI3K-Akt、癌症、AGE-RAGE等信号通路，治疗胃黏膜IM。

Abstract:

Abstract：Objective：To analyze the potential mechanism of Hewei Huashi Decoction in the treatment of gastric intestinal metaplasia （IM） based on network pharmacology and molecular docking technology. Methods： The active components and potential targets of Hewei Huashi Decoction were retrieved using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and HERB databases. Gastric IM-related targets were obtained from the Human Gene Database （GeneCards） and Online Mendelian Inheritance in Man （OMIM） databases. The intersection of these two sets of targets yielded potential therapeutic targets. A protein-protein interaction （PPI） network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING） database，and core targets were identified using Cytoscape software. Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed using the Metascape database. Finally，molecular docking software such as PyMOL and AutoDock was performed to validate the binding affinity between key active components and core targets. Results： A total of 130 active components of Hewei Huashi Decoction were screened， corresponding to 488 targets； 1 987 gastric IM-related targets were identified， and 186 potential therapeutic targets were obtained. Key active components including quercetin， β-sitosterol， naringenin， and luteolin， as well as core targets such as tumor protein p53 （TP53）， protein kinase B1 （AKT1）， interleukin-6 （IL-6）， tumor necrosis factor （TNF）， and epidermal growth factor receptor （EGFR） were identified. Enrichment analysis showed that these potential therapeutic targets were significantly enriched in the phosphatidylinositol 3-kinase （PI3K）-Akt signaling pathway， pathways in cancer， and the advanced glycation end products-receptor for advanced glycation end products （AGE-RAGE） signaling pathway in diabetic complications， involving biological processes such as cell proliferation， apoptosis， and inflammatory response. Molecular docking results showed that the binding energies between key active components and core targets ranged from -8.16 to -4.97 kcal/mol. Conclusion： In the treatment of gastric IM ， Hewei Huashi Decoction acts synergistically through key active components such as quercetin ， β-sitosterol， naringenin， and luteolin on core targets including TP53， AKT1， IL-6， TNF， and EGFR， thereby regulating signaling pathways such as PI3K-Akt，cancer，and AGE-RAGE.