目的 運(yùn)用網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)探討仙鶴草改善慢性萎縮性胃炎的物質(zhì)基礎(chǔ)及作用機(jī)制。方法 通過TCMSP數(shù)據(jù)庫篩選仙鶴草的活性成分并預(yù)測其作用靶點(diǎn)；通過GeneCards、OMIM數(shù)據(jù)庫篩選慢性萎縮性胃炎相關(guān)靶點(diǎn)；將活性成分靶點(diǎn)與慢性萎縮性胃炎靶點(diǎn)取交集，通過String 12.0數(shù)據(jù)庫構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)，并運(yùn)用Cytoscape 3.10.1軟件構(gòu)建“中藥–疾病–化合物–交集靶標(biāo)”網(wǎng)絡(luò)圖；通過R軟件對核心靶點(diǎn)進(jìn)行基因本體（GO）和京都基因與基因組百科全書（KEGG）富集分析以預(yù)測作用機(jī)制；通過AutoDock軟件進(jìn)行分子對接驗(yàn)證。結(jié)果 從仙鶴草中篩選出5個(gè)活性成分，作用于90個(gè)靶點(diǎn)，其中仙鶴草改善慢性萎縮性胃炎的核心活性成分為鞣花酸、山柰酚、兒茶素、木犀草素、槲皮素；核心靶點(diǎn)為B淋巴細(xì)胞瘤-2（Bcl-2）、半胱氨酸天冬氨酸蛋白酶-3（CASP3）、表皮生長因子受體（EGFR）、缺氧誘導(dǎo)因子-1A（HIF-1A）、原癌基因（MYC）等；作用機(jī)制主要涉及抗腫瘤、調(diào)節(jié)免疫、調(diào)節(jié)脂代謝、抗病毒等多條信號通路；分子對接顯示，仙鶴草核心活性成分與核心靶點(diǎn)具有較高親和力。結(jié)論 仙鶴草可能通過調(diào)節(jié)細(xì)胞增殖、凋亡、炎癥、代謝等相關(guān)基因及通路發(fā)揮多靶點(diǎn)、多通路的治療作用。

Objective To explore the material basis and action mechanisms of Agrimoniae Herba in treatment of chronic atrophic gastritis based on network pharmacology and molecular docking techniques. Methods To screen the active ingredient of Agrimoniae Herba from the TCMSP database, and predict their target proteins. To obtain the relevant target associated with chronic atrophic gastritis from the GeneCards and OMIM databases. The intersection of target proteins between the active ingredient of Agrimoniae Herba and chronic atrophic gastritis was used to construct a PPI network via String 12.0. The network diagram of “TCM - disease - compound - intersection target” was constructed using Cytoscape 3.10.1 software. Core target proteins were subjected to GO and KEGG enrichment analysis using R software to predict the underlying mechanisms. Molecular docking was performed using AutoDock software to validate the interactions. Results Five active components were selected from Agrimoniae Herba, targeting 90 proteins. Among them, the core active components responsible for improving chronic atrophic gastritis were identified as ellagic acid, kaempferol, epicatechin, apigenin, and quercetin. Core target proteins included Bcl-2, CASP3, EGFR, HIF-1A, and MYC. The action mechanisms mainly involved multiple signaling pathways such as anti-tumor effects, immune regulation, lipid metabolism regulation, and antiviral activities. Molecular docking results demonstrated high affinity between the core active components of Agrimoniae Herba and the core target proteins. Conclusion This study unveils that Agrimoniae Herba may exert a multi-target, multi-pathway therapeutic effect through the regulation of genes and pathways associated with cell proliferation, apoptosis, inflammation, and metabolism.

國家重點(diǎn)研發(fā)計(jì)劃課題（2017YFC1700601）；武漢市中醫(yī)藥科研項(xiàng)目（WZ22Q28）；武漢市醫(yī)學(xué)科研項(xiàng)目（WZ20A07）