目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)探討蛇床子治療濕疹的可能作用靶點(diǎn)及機(jī)制。方法 采用口服生物利用度（OB）≥30%，類藥性（DL）≥0.18為閾值，在TCMSP和SwissTargetPrediction平臺(tái)篩選蛇床子的主要化學(xué)成分及其作用靶點(diǎn)；以“eczema”為關(guān)鍵詞，借助GeneCards、DisGeNET數(shù)據(jù)庫(kù)獲取與濕疹相關(guān)的疾病靶點(diǎn)；Venny 2.1.0獲取蛇床子組分靶點(diǎn)與濕疹的共有靶點(diǎn)；采用Cytoscape 3.9.0軟件構(gòu)建“蛇床子–化學(xué)成分–作用靶點(diǎn)”網(wǎng)絡(luò)圖，并根據(jù)網(wǎng)絡(luò)圖中度（degree）值，篩選出蛇床子治療濕疹的核心活性成分；利用STRING數(shù)據(jù)庫(kù)及Cytoscape 3.9.0軟件構(gòu)建交集靶點(diǎn)的蛋白相互作用（PPI）網(wǎng)絡(luò)圖并篩選核心靶點(diǎn)；基于Omicshare云平臺(tái)對(duì)交集靶點(diǎn)的基因本體論（GO）與京都基因與基因組百科全書（KEGG）富集分析，預(yù)測(cè)蛇床子治療濕疹的潛在作用通路，最后通過(guò)分子對(duì)接技術(shù)驗(yàn)證活性成分與核心靶點(diǎn)的結(jié)合能力。結(jié)果 篩選出蛇床子化學(xué)成分20個(gè)，化學(xué)成分靶點(diǎn)與濕疹疾病共同靶點(diǎn)33個(gè)?！吧叽沧莹C化學(xué)成分–共有靶點(diǎn)-濕疹”網(wǎng)絡(luò)圖篩選核心化合物3個(gè)，分別為香葉木素、花椒油素N、6-香葉基-7-羥基香豆素。PPI網(wǎng)絡(luò)拓?fù)浞治龊蚄EGG通路富集分析發(fā)現(xiàn)蛇床子可通過(guò)作用于腫瘤壞死因子（TNF）信號(hào)通路及蛋白激酶B1（AKT1）、基質(zhì)金屬蛋白酶9（MMP9）、磷脂酰肌醇3-激酶調(diào)節(jié)亞基1（PIK3R1）、血管細(xì)胞黏附分子1（VCAM1）、胞間黏附分子-1（ICAM1）、磷脂酰肌醇-3-激酶催化亞基α（PIK3CA）等核心靶點(diǎn)發(fā)揮治療濕疹的作用。分子對(duì)接進(jìn)一步驗(yàn)證主要成分和關(guān)鍵靶點(diǎn)的相互作用，其中香葉木素、花椒油素N、6-香葉基-7-羥基香豆素與核心靶點(diǎn)MMP9、AKT1的對(duì)接親和度較高。結(jié)論 網(wǎng)絡(luò)藥理學(xué)聯(lián)用分子對(duì)接技術(shù)揭示蛇床子可以通過(guò)多成分、多靶點(diǎn)、多途徑改善濕疹，為其進(jìn)一步深入研究及臨床應(yīng)用提供新思路與理論依據(jù)。

Objective To explore the possible targets and mechanisms of Cnidii Fructus in treatment of eczema by network pharmacology and molecular docking technique. Methods Taking oral bioavailability (OB) ≥ 30% and drug-like (DL) ≥ 0.18 as the thresholds, the main chemical constituents of Cnidii Fructus and the corresponding targets were obtained from TCMSP and SwissTargetPrediction databases. Using “eczema” as the key word, the eczema-related disease targets were obtained with the help of GeneCards and DisGeNET databases. Venny 2.1.0 obtained the common targets of Fructus Cnidii and eczema. The “Cnidii Fructus -chemical compounds -common targets -eczema” network was constructed by Cytoscape 3.9.0 software and then the core active ingredients of Cnidii Fructus for the treatment of eczema were screened out. STRING database and Cytoscape 3.9.0 software were used to construct the PPI network of the intersection targets, and the core targets were obtained. GO and KEGG enrichment analysis of the intersection targets was performed using the Omicshare platform to predict the potential mechanism of Cnidii Fructus against eczema, and the binding ability of active ingredients to core targets was further verified by molecular docking. Results 20 chemical constituents of Cnidii Fructus were screened out, and 33 intersection targets between Cnidii Fructus and eczema were obtained. 3 core compounds were acquired from “Cnidii Fructus-chemical compounds-common targets-eczema” network, which were diosmetin, xanthoxylin N and ostruthin. Topology analysis of PPI network and KEGG pathway enrichment analysis showed that Cnidii Fructus alleviated eczema mainly acting on the TNF signaling pathway and the core targets AKT1, MMP9, PIK3R1, VCAM1, ICAM1, PIK3CA, etc. The molecular docking results verified the interaction between the active ingredients and the core targets. The docking affinity among diosmetin, xanthoxylin N, and ostruthin and the core targets MMP-9, AKT1 were the highest. Conclusion Network pharmacology combined with molecular docking proved that Cnidii Fructus could improve eczema through multi-component, multi-target and multi-pathway, which provides new ideas and theoretical basis for its further in-depth research and clinical application.

R966

國(guó)家自然科學(xué)基金資助項(xiàng)目（82104312）；中央高?；究蒲袠I(yè)務(wù)費(fèi)專項(xiàng)資金資助項(xiàng)目（2042022kf1077）