目的 基于網(wǎng)絡(luò)藥理學(xué)結(jié)合譜效關(guān)系及分子對接，探討五味甘露抗炎的物質(zhì)基礎(chǔ)及作用機(jī)制。方法 利用中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫與分析平臺（TCMSP）、Genecards、Pubchem、UniProt、中國學(xué)術(shù)期刊全文數(shù)據(jù)庫（CNKI）等數(shù)據(jù)庫篩選五味甘露的活性成分及抗炎的作用靶點，利用STRING數(shù)據(jù)庫、Cytoscape3.7軟件構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)并篩選核心靶點，利用Metascape數(shù)據(jù)庫進(jìn)行基因本體（GO）及京都基因與基因組百科全書（KEGG）通路富集分析。將細(xì)胞炎癥模型與高效液相色譜法相結(jié)合分析五味甘露不同極性部位的抗炎活性和藥效成分。采用Discovery Studio Lib Dock軟件將主要藥效成分與核心靶點進(jìn)行分子對接，并進(jìn)行可視化分析。結(jié)果 網(wǎng)絡(luò)藥理學(xué)分析共獲取五味甘露抗炎成分125個，潛在抗炎靶點251個，得到核心靶點131個，包括腫瘤壞死因子（TNF）、白細(xì)胞介素-6（IL-6）、白細(xì)胞介素-1β（IL-1β）重要靶點。KEGG通路富集分析，共富集到20條相關(guān)通路，其中涉及基因較多的包括脂質(zhì)與動脈粥樣硬化和類風(fēng)濕性關(guān)節(jié)炎（RA）等通路，諸多通路均涉及NOD樣受體熱蛋白結(jié)構(gòu)域相關(guān)蛋白3（NLRP3）核心靶點。五味甘露的醋酸乙酯相能夠抑制炎癥相關(guān)的NLRP3、IL-1β、TNF的表達(dá)，且其中總黃酮含量最高，為（305.0±11.4）mg·g^-1。LC-MS圖譜分析和分子對接實驗顯示醋酸乙酯相中山柰酚、楊梅素、異葒草素、異槲皮苷和黃芪苷等黃酮類物質(zhì)的離子強(qiáng)度遠(yuǎn)遠(yuǎn)高于單味藥材且其母核結(jié)構(gòu)與NLRP3受體蛋白的7個氨基酸活性位點有顯著的相互作用。結(jié)論 五味甘露抗炎的主要物質(zhì)為黃酮類，可通過抑制NLRP3炎癥小體的活化起到抗炎作用。

Objective To explore the material basis and mechanism of Wuwei Ganlu on anti-inflammatory based on network pharmacology combined with spectrum effect relationship and molecular docking. Methods The active ingredients and antiinflammatory targets of Wuwei Ganlu were obtained using databases such as TCMSP, Genecards, Pubchem, UniProt, and CNKI, then core targets and protein interaction networks were screened by STRING database and Cytoscape 3.7 software. Metascape was used to perform GO and KEGG signal pathway enrichment of core targets. Subsequently, the cellular inflammation model combined with high-performance liquid chromatography was used to analyze the anti-inflammatory activity and pharmacological components of different polar parts of Wuwei Ganlu. Finally, discovery Studio Lib Dock software was applied to connect the main pharmacological components with the core targets for molecular docking and visual analysis. Results Through network pharmacological analysis, a total of 125 anti-inflammatory components of Wuwei Ganlu and 251 potential anti-inflammatory targets, as well as 131 core targets were obtained, including TNF, IL-6, IL-1β. The KEGG pathway enrichment analysis enriched 20 related pathways, including lipid and atherosclerosis, and rheumatoid arthritis pathways, which all involved NLRP3 core targets. In addition, the ethyl acetate phase of Wuwei Ganlu can inhibit the expression of NLRP3, IL-1β and TNF with a total flavonoid content of (305 ±11.4) mg·g^-1. LC-MS spectrum analysis and molecular docking experiments showed that the ion strength of flavonoids such as naphthol, myricetin, isoquercetin, isoquercetin, and astragaloside in the ethyl acetate phase was much higher than that of single medicinal herbs, and their mother nucleus structure had significant interactions with the seven amino acid active sites of the NLRP3 receptor protein. Conclusion The main anti-inflammatory substances of Wuwei Ganlu are flavonoids, which can exert antiinflammatory effects by inhibiting the activation of NLRP3 inflammasomes.

R285.5

國家自然科學(xué)基金-面上項目（82170424）;國家自然科學(xué)基金-青年項目（81700364）;藏醫(yī)藥“十四五”規(guī)劃內(nèi)涵建設(shè)一期項目（2021zyygh002）;2020年中醫(yī)學(xué)（藏醫(yī)）博士點建設(shè)科研支撐計劃項目（BSDJS-20-05）