基于网络药理学和分子对接探讨二陈汤治疗慢性萎缩性胃炎的作用机制

Mechanism of Erchen Decoction in the Treatment of Chronic Atrophic Gastritis Based on Network Pharmacology and Molecular Docking

目的:利用网络药理学与分子对接的方法,探讨二陈汤对于治疗慢性萎缩性胃炎的潜在作用机制。方法:使用中药系统药理学数据库与分析平台预测二陈汤的活性成分,运用GeneCards、人类孟德尔遗传综合数据库和治疗靶点数据库筛选得到慢性萎缩性胃炎的相关作用靶点,运用STRING平台和Cytoscape 3.8.2软件构建蛋白质-蛋白质相互作用作用网络,通过DAVID平台对关键靶点进行京都基因与基因组百科全书(KEGG)通路富集分析和基因本体功能富集分析,运用SwissDock平台预测核心活性化合物与关键靶点的结合程度。结果:筛选得到二陈汤中关键化合物127个,成分靶点246个,疾病靶点892个,交集得到二陈汤与慢性萎缩性胃炎的共有靶点95个。筛选出槲皮素、山柰酚、黄芩苷、甘草查尔酮A、柚皮素、异鼠李素和β-谷甾醇等关键活性成分,并分别与8个关键靶点蛋白激酶B1、肿瘤蛋白p53、白细胞介素(IL)6、肿瘤坏死因子(TNF)、血管内皮生长因子A、IL-1β、前列腺素G/H合酶2和胱天蛋白酶3有良好的结合度。KEGG分析结果显示,二陈汤通过癌症信号通路、化学致癌-活性氧类信号通路和TNF信号通路等多条通路治疗慢性萎缩性胃炎。结论:二陈汤对慢性萎缩性胃炎的治疗是通过多成分、多靶点、多通路协同发挥作用的,网络药理学和分子对接结果可为后续对慢性萎缩性胃炎的治疗与研究提供依据。

OBJECTIVE:To explore the potential mechanism of Erchen decoction in the treatment of chronic atrophic gastritis based on network pharmacology and molecular docking.METHODS:Traditional Chinese medicine systems pharmacology database and analysis platform was used to predict the active components of Erchen decoction,GeneCards,online Mendelian inheritance in man and therapeutic target database were used to screen the related targets of chronic atrophic gastritis.The protein-protein interaction network was constructed by using STRING platform and Cytoscape 3.8.2.Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis and gene ontology functional enrichment analysis were performed on key targets through the DAVID platform.The binding degree of core active compounds to key targets was predicted by the SwissDock platform.RESULTS:Totally 127 key compounds,246 component targets and 892 disease targets were identified in Erchen decoction,and 95 common targets were obtained by intersection of Erchen decoction and chronic atrophic gastritis.Key active components such as quercetin,kaempferol,baicalin,glycyrrhizin A,naringin,isorhamnetin andβ-sitosterol were screened,and had good binding with 8 key targets such as protein kinase B1,tumor protein p53,interleukin(IL)6,tumor necrosis factor(TNF),vascular endothelial growth factor A,IL-1β,prostaglandin G/H synthase 2 and caspase 3.KEGG results showed that Erchen decoction in the treatment of chronic atrophic gastritis through multiple pathways including cancer signaling pathway,chemical carcinogenesis-activated oxygen species signaling pathway and TNF signaling pathway.CONCLUSIONS:Erchen decoction plays a synergistic role in the treatment of chronic atrophic gastritis through multi-component,multi-target and multi-signaling pathway,and the results of network pharmacology and molecular docking can provide basis for the subsequent treatment and research of chronic atrophic gastritis.