目的 利用網(wǎng)絡藥理學和分子對接方法研究甘草治療白癜風的作用靶點和機制。方法 使用中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）篩選得到甘草中的活性成分，使用SwissTargetPrediction數(shù)據(jù)庫預測各個活性成分的作用靶點；通過OMIM、GeneCards數(shù)據(jù)庫獲取白癜風的相關靶點，與活性成分作用靶點取交集；利用Cytoscape 3.9.1軟件對交集靶點進行拓撲學分析并篩選得到甘草主要活性成分，構建得到“甘草主要活性成分–白癜風靶點”網(wǎng)絡；將甘草活性成分和白癜風的交集靶點導入String數(shù)據(jù)庫構建靶點間的蛋白相互作用（PPI）網(wǎng)絡；使用Metascape數(shù)據(jù)庫對潛在作用靶點進行基因本體（GO）功能富集分析和京都基因與基因組百科全書（KEGG）通路富集分析；使用AutoDockTools 1.5.7軟件進行分子對接驗證并使用PyMol軟件對結果進行可視化處理。結果 共篩選得到谷甾醇、格里西輪、光果甘草寧、甘草查爾酮B、刺芒柄花黃素等84個活性成分，作用于8 400個潛在靶點，白癜風相關靶點1 349個，甘草–白癜風的交集靶點133個；PPI網(wǎng)絡分析得到蛋白激酶B1（Akt1）、信號傳導和轉錄激活蛋白3（STAT3）、腫瘤壞死因子（TNF）、白細胞介素-6（IL-6）、有絲分裂原活化蛋白激酶1（MAPK1）、血管內(nèi)皮生長因子A（VEGFA）6個核心作用靶點；GO和KEGG富集分析顯示，甘草治療白癜風主要涉及病毒感染、癌癥、細胞凋亡、乙型肝炎、細胞衰老等信號通路。分子對接結果顯示谷甾醇、格里西輪、光果甘草寧、(2S)-7-羥基-2-(4-羥基苯基)-8-(3-甲基丁烯-2-乙烯基)色曼-4-酮、甘草查耳酮B、刺芒柄花黃素6個核心成分與核心靶點具有較好的結合能。結論 甘草可能通過調(diào)控細胞衰老和凋亡、免疫功能、炎癥等多個方面發(fā)揮治療白癜風的作用，為后續(xù)研究甘草治療白癜風提供參考。

Objective To study the target and mechanism of Glycyrrhizae Radix et Rhizoma in treatment of vitiligo based on network pharmacology and molecular docking. Methods Active components in Glycyrrhizae Radix et Rhizoma were screened by TCMSP, and the targets of each active component were predicted by SwissTargetPrediction database. The related targets of vitiligo were obtained through OMIM and GeneCards databases, and the targets of active components were intersected. Cytoscape 3.9.1 software was used to perform topological analysis on the intersection targets and screen out the main active components of Glycyrrhizae Radix et Rhizoma, and the network of Glycyrrhizae Radix et Rhizoma main active components - vitiligo target was constructed. Intersection targets of Glycyrrhizae Radix et Rhizoma active components and vitiligo were imported into the String database to construct PPI network between targets. Metascape database was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis on potential targets. AutoDockTools 1.5.7 software was used for molecular docking verification and PyMol software was used to visualize the results. Results A total of 84 active ingredients such as sitosterol, glisiran, guangguo gancaoning, licochalcone B, formononetin and so on were screened, which acted on 8 400 potential targets, 1 349 vitiligo related targets, and 133 Glycyrrhizae Radix et Rhizom- vitiligo intersection targets. Six core targets of Akt1, STAT3, TNF, IL96, MAPK1, and VEGFA were obtained by PPI network analysis. GO and KEGG enrichment analysis showed that Glycyrrhizae Radix et Rhizom in treatment of vitiligo mainly involved signal pathways such as viral infection, cancer, apoptosis, hepatitis B, and cell senescence. The results of molecular docking showed that the seven core components of sitosterol, glycyrin, glabranin, (2S)-6-(2,4-dihydroxyphenyl)-2-(2-hydroxypropan-2-yl)-4-methoxy-2,3-dihydrofuro [3,2-g]chromen-7-one, licochalcone B, formononetin had good binding energy with the core targets. Conclusion Glycyrrhizae Radix et Rhizom may play a role in treatment of vitiligo by regulating cell senescence and apoptosis, immune function, inflammation and other aspects, which provides a reference for the follow-up study of Glycyrrhizae Radix et Rhizom in treatment of vitiligo.

R285

國家重點研發(fā)計劃項目(2018YFC1706500)