目的 基于超高效液相色譜–四級桿–飛行時間串聯(lián)質(zhì)譜（UHPLC-Q-TOF-MS）法、網(wǎng)絡藥理學和分子對接驗證探討金蓮花抗炎的藥效物質(zhì)及機制。方法 根據(jù)質(zhì)譜信息結合對照品、文獻和數(shù)據(jù)庫指認金蓮花中化學成分信息；借助Swiss ADME平臺及查詢文獻來篩選金蓮花潛在活性成分；通過Swiss Target Prediction數(shù)據(jù)庫預測金蓮花活性成分的作用靶點；采用OMIM、GeneCards、DrugBank、DisGeNET數(shù)據(jù)庫獲取炎癥的相關靶點；利用Venn圖取藥物活性成分靶點與疾病靶點交集后，用STRING數(shù)據(jù)庫構建蛋白質(zhì)相互作用網(wǎng)絡（PPI）；用Metascape數(shù)據(jù)庫對核心靶點進行基因本體論（GO）富集分析和京都基因與基因組百科全書（KEGG）通路分析；借助Cytoscape軟件構建“活性成分–炎癥靶點–富集通路”網(wǎng)絡；采用分子對接技術進行初步驗證。結果 從金蓮花中共鑒別出38個化合物，包括黃酮類23個，有機酸類10個，香豆素類1個，單糖2個以及苯乙素類2個；網(wǎng)絡藥理學研究表明，金蓮花可能通過鼠尾草素、薊黃素、香葉木素、阿魏酸、槲皮素和芹菜素等成分，作用于腫瘤壞死因子（TNF）、蛋白激酶B1（Akt1）、血管內(nèi)皮生長因子A（VEGFA）、前列腺素內(nèi)過氧化物合酶2（PTGS2）、表皮生長因子受體（EGFR）、酪氨酸蛋白激酶（SRC）等核心靶點，來調(diào)節(jié)癌癥中的途徑（pathways in cancer）、血脂與動脈粥樣硬化（lipid and atherosclerosis）、磷脂酰肌醇-3-激酶（PI3K）/Akt、TNF、白細胞介素-17（IL-17）、絲裂原活化蛋白激酶（MAPK）、晚期糖基化終末產(chǎn)物-糖基化終末產(chǎn)物受體（AGE-RAGE）、缺氧誘導因子-1（HIF-1）等信號通路，從而發(fā)揮抗炎作用；分子對接驗證結果表明，金蓮花抗炎藥效成分與疾病靶點蛋白具有較強的結合活性。結論 揭示了金蓮花通過多成分、多靶點、多通路聯(lián)合發(fā)揮抗炎作用的機制，為后續(xù)臨床應用提供科學合理的理論基礎。

Objective To explore the anti-inflammation material basis and mechanism of Trollius chinensis Bge. based on UHPLC-Q-TOF-MS, network pharmacology and molecular docking verification. Methods The chemical constituents of Trollius chinensis Bge. were identified according to the information of mass spectrometry combined with the standard, literature and database. Using Swiss ADME platform and literature inquiry to screen the potential active ingredients of Trollius chinensis Bge. Predicted the target of active components of Trollius chinensis Bge.by Swiss Target Prediction database. The relevant targets of inflammation were obtained from OMIM, GeneCards, DrugBank, and DisGeNET databases. After the intersection of drug active ingredient targets and disease targets was obtained using Venn diagram, protein-protein interaction network (PPI) was constructed by using STRING database. GO enrichment analysis and KEGG pathway analysis were carried out through the Metascape database. The network of "active ingredients-inflammation targets-enrichment pathways" was constructed with the Cytoscape software. Molecular docking technology was used for preliminary verification. Results A total of 38 compounds were identified from Trollius chinensis Bge. including 23 flavonoids, 10 organic acids, 1 coumarin, 2 monosaccharides and 2 styrenes. Network pharmacological research showed that Trollius chinensis Bge. may acted on TNF, Akt1, VEGFA, PTGS2, EGFR, SRC and other core targets through salvigenin, cirsimaritin, diosmetin, ferulic acid, quercetin, apigenin and other active compounds, regulating pathways in cancer, lipid and atherosclerosis, PI3K/Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, HIF-1 signaling pathway and other pathways, thus exert anti-inflammation effects. The results of molecular docking verification showed that the anti-inflammation components of Trollius chinensis Bge. had strong binding activity with disease target proteins. Conclusion Preliminatively revealing the anti-inflammation effects of Trollius chinensis Bge. through the combination of multi-components, multi-targets and multi-pathways, providing a scientific and reasonable theoretical basis for subsequent clinical application.

R285.5

中國中醫(yī)科學院中央本級重大增減支項目（2060302）