目的 基于网络药理学和分子对接技术探讨布渣叶Microcos paniculata Linn.对消化不良的潜在物质基础和作用机制。方法 通过检索TCMSP数据库、文献和SwissTargetPredicted数据库收集成分和靶点信息,利用GeneCards和OMIM数据库获得疾病靶点,利用软件R 4.2.1中Venndigram包构建韦恩图,获得布渣叶和疾病的共同靶点;将得到的共同靶点通过软件R 4.2.1做基因本体(GO)和京都基因和基因组百科全书(KEGG)分析,通过STRING网站和Cytoscape 3.9.2做PPI分析得到核心靶点;利用Cytoscape 3.9.2构建“成分-靶点”网络图获得核心成分,将获得的核心成分和核心靶点利用Mastro进行分子对接。结果 筛出154个靶点,核心靶点主要有蛋白激酶B1(Akt1)、细胞肿瘤抗原(TP53)、血管内皮生长因子(VEGFA)、表皮生长因子受体(EGFR)、白细胞介素-6(IL-6)、非受体酪氨酸激酶(SRC)、肿瘤坏死因子(TNF),布渣叶改善消化不良可能通过正向调节酶活性、伤口愈合、丝裂原活化蛋白激酶(MAPK)级联调控等生物过程,与磷脂酰激醇3-激酶(PI3K)-Akt信号通路、脂质代谢与动脉粥样硬化通路、流体剪切应力和动脉粥样硬化有关。分子对接结果表明,核心靶点与相对应的核心成分有比较稳定的对接,其中紫云英苷与SRC有强烈的对接活性。结论 布渣叶中多种活性成分通过多途径、多靶点来调节胃肠动力、修复胃肠黏膜屏障、抑制肠道炎症反应以发挥药效,可为后续进一步作用机制和物质基础研究提供一定的参考。

Objective To explore the material basis and potential mechanism of leaves of Microcos paniculata Linn. in treatment of dyspepsia based on network pharmacology and molecular docking technology. Method Component information was collected from TCMSP database, literature, and SiwissTargetPredicted database. Disease targets of dyspepsia were obtained from GeneCards and OMIM databases. Venn digram package in R 4.2.1 was used to construct the Venndigram diagram to obtain the common target of leaves of Microctis Folium and diseases. GO analysis and KEGG analysis were construct through putting the common targets into the R 4.2.1 and then key targets were got through madeing PPI analysis using STRING website and Cytoscape software. The key components were extracted by constructing “componets-targets” network chart with cytoscape 3.9.2 and then applyed to perform molecular docking.Results A total of 154 common targets were screened out, and the core targets were mainly Akt1, TP53, IL-6,VEGFA, EGFR, SRC, TNF. As showed as GO analysis, positive regulation of kinase activity, wound healing and MAPK cascade regulation were involved. KEGG analysis mainly involved PI3K-Akt signaling pathway, lipid and atherosclerosis, fluid shear stress and atherosclerosis. Molecular docking results showed that the core targets had relatively stable docking with the corresponding core components, especially astragalin has strong docking activity with SRC.Conclusion Multiple componets of leaves of Microcos paniculata mainly regulated gastrointestinal motility, repaired gastrointestinal mucosal barrier and inhibited intestinal inflammation to treat dyspepsia through multiple pathways and multiple targets, providing certain reference for further research on the mechanism and material basis.

R975

广东省医学科研基金资助项目(A2022479);中山市科技计划资助项目(20082A111)