目的 通過(guò)網(wǎng)絡(luò)藥理學(xué)、分子對(duì)接和分子動(dòng)力學(xué)模擬（MD）探討黃連治療潰瘍性結(jié)腸炎的作用機(jī)制。方法 利用TCMSP和UniProt數(shù)據(jù)庫(kù)獲取黃連活性成分及其對(duì)應(yīng)靶點(diǎn)，經(jīng)GeneCards、OMIM、Drugbank、TTD、DisGeNET數(shù)據(jù)庫(kù)篩選潰瘍性結(jié)腸炎相關(guān)靶點(diǎn)，利用Venny 2.1.0獲取黃連和潰瘍性結(jié)腸炎的交集靶點(diǎn)，并上傳String 11.0數(shù)據(jù)庫(kù)繪制蛋白相互作用（PPI）網(wǎng)絡(luò)圖。通過(guò)Cytoscape3.9.0的Cyto Hubb插件和“藥物活性成分–靶點(diǎn)–通路網(wǎng)絡(luò)圖”篩選核心靶點(diǎn)。借助Metascape數(shù)據(jù)庫(kù)對(duì)交集靶點(diǎn)進(jìn)行基因本體功能注釋?zhuān)℅O）及京都基因與基因組百科全書(shū)（KEGG）通路富集分析。通過(guò)Autodock Tools 1.5.6軟件將活性成分與核心靶點(diǎn)進(jìn)行分子對(duì)接。用分子動(dòng)力學(xué)模擬法驗(yàn)證最佳結(jié)合模型的穩(wěn)定性。結(jié)果 共篩選出黃連7個(gè)活性成分及其137個(gè)靶點(diǎn)，潰瘍性結(jié)腸炎1 258個(gè)相關(guān)靶點(diǎn)和81個(gè)交集靶點(diǎn)。核心靶點(diǎn)包括蛋白激酶B1（Akt1）、B淋巴細(xì)胞2（BCL2）、有絲分裂原活化蛋白激酶1（MAPK1）等。生物過(guò)程包括無(wú)機(jī)物的反應(yīng)、細(xì)胞因子受體結(jié)合等。KEGG通路富集主要包括MAPK信號(hào)通路等。分子對(duì)接結(jié)果顯示，黃連的核心活性成分能夠很好地與關(guān)鍵靶點(diǎn)結(jié)合。MD進(jìn)一步驗(yàn)證了能量結(jié)合最好的小檗堿與白細(xì)胞介素（IL）-1β的結(jié)合能為−36.19 kJ/mol。結(jié)論 黃連可能通過(guò)多成分、多靶點(diǎn)及多通路參與潰瘍性結(jié)腸炎的治療。

Objective To investigate the mechanism of Coptis chinensis in treatment of ulcerative colitis by network pharmacology, molecular docking, and molecular dynamics simulation (MD). Methods The active ingredients of Coptis chinensis and its corresponding targets were obtained by TCMSP and UniProt databases. The targets related to ulcerative colitis were screened by GeneCards, OMIM, Drugbank, TTD, and DisGeNET databases. The intersection targets of Coptis chinensis and ulcerative colitis were obtained by Venny 2.1.0. The String 11.0 database was uploaded to map the protein interaction (PPI) network. Core targets are screened using the Cyto Hubb plugin of Cytoscape3.9.0 and the drug active ingredients–target–pathway network diagram. The gene ontology Function annotation (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for the intersection targets using Metascape database. Molecular docking of the active ingredient with the core target was performed using Autodock Tools 1.5.6 software. The stability of the optimal binding model was verified by molecular dynamics simulation. Results A total of 7 active ingredients and 137 targets of Coptis chinensis, 1 258 associated targets and 81 intersection targets of ulcerative colitis were screened. Core targets include Akt1, BCL2, MAPK1, etc. Biological processes include the reaction of inorganic substances, cytokine receptor binding, etc. The enrichment of KEGG pathway mainly includes MAPK signaling pathway and so on. The results of molecular docking showed that the core active components of Coptis chinensis could combine well with key targets. MD further verified that the binding energy of berberine with IL-1β with the best energy binding capacity was −36.19 kJ/mol. Conclusion It is suggested that Coptis chinensis may treat ulcerative colitis by acting through a multi-component, multi-target, and multi-pathway mechanism.

R285

云南省科技廳科技計(jì)劃項(xiàng)目(202101AZ070001-268);昆明市衛(wèi)生健康委員會(huì)衛(wèi)生科研課題項(xiàng)目(2022-04-01-009);昆明市衛(wèi)生科技人才培養(yǎng)項(xiàng)目暨“十百千”工程(2022-SW(后備)-60)