目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)探討布渣葉Microcos paniculata Linn.對消化不良的潛在物質(zhì)基礎(chǔ)和作用機制。方法 通過檢索TCMSP數(shù)據(jù)庫、文獻和SwissTargetPredicted數(shù)據(jù)庫收集成分和靶點信息,利用GeneCards和OMIM數(shù)據(jù)庫獲得疾病靶點,利用軟件R 4.2.1中Venndigram包構(gòu)建韋恩圖,獲得布渣葉和疾病的共同靶點;將得到的共同靶點通過軟件R 4.2.1做基因本體(GO)和京都基因和基因組百科全書(KEGG)分析,通過STRING網(wǎng)站和Cytoscape 3.9.2做PPI分析得到核心靶點;利用Cytoscape 3.9.2構(gòu)建“成分-靶點”網(wǎng)絡(luò)圖獲得核心成分,將獲得的核心成分和核心靶點利用Mastro進行分子對接。結(jié)果 篩出154個靶點,核心靶點主要有蛋白激酶B1(Akt1)、細胞腫瘤抗原(TP53)、血管內(nèi)皮生長因子(VEGFA)、表皮生長因子受體(EGFR)、白細胞介素-6(IL-6)、非受體酪氨酸激酶(SRC)、腫瘤壞死因子(TNF),布渣葉改善消化不良可能通過正向調(diào)節(jié)酶活性、傷口愈合、絲裂原活化蛋白激酶(MAPK)級聯(lián)調(diào)控等生物過程,與磷脂酰激醇3-激酶(PI3K)-Akt信號通路、脂質(zhì)代謝與動脈粥樣硬化通路、流體剪切應(yīng)力和動脈粥樣硬化有關(guān)。分子對接結(jié)果表明,核心靶點與相對應(yīng)的核心成分有比較穩(wěn)定的對接,其中紫云英苷與SRC有強烈的對接活性。結(jié)論 布渣葉中多種活性成分通過多途徑、多靶點來調(diào)節(jié)胃腸動力、修復(fù)胃腸黏膜屏障、抑制腸道炎癥反應(yīng)以發(fā)揮藥效,可為后續(xù)進一步作用機制和物質(zhì)基礎(chǔ)研究提供一定的參考。

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

廣東省醫(yī)學(xué)科研基金資助項目(A2022479);中山市科技計劃資助項目(20082A111)