目的 基于網(wǎng)絡藥理學和分子對接技術探討蛇床子治療濕疹的可能作用靶點及機制。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平臺篩選蛇床子的主要化學成分及其作用靶點；以“eczema”為關鍵詞，借助GeneCards、DisGeNET數(shù)據(jù)庫獲取與濕疹相關的疾病靶點；Venny 2.1.0獲取蛇床子組分靶點與濕疹的共有靶點；采用Cytoscape 3.9.0軟件構建“蛇床子–化學成分–作用靶點”網(wǎng)絡圖，并根據(jù)網(wǎng)絡圖中度（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)庫及Cytoscape 3.9.0軟件構建交集靶點的蛋白相互作用（PPI）網(wǎng)絡圖并篩選核心靶點；基于Omicshare云平臺對交集靶點的基因本體論（GO）與京都基因與基因組百科全書（KEGG）富集分析，預測蛇床子治療濕疹的潛在作用通路，最后通過分子對接技術驗證活性成分與核心靶點的結合能力。結果 篩選出蛇床子化學成分20個，化學成分靶點與濕疹疾病共同靶點33個。“蛇床子–化學成分–共有靶點-濕疹”網(wǎng)絡圖篩選核心化合物3個，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)絡拓撲分析和KEGG通路富集分析發(fā)現(xiàn)蛇床子可通過作用于腫瘤壞死因子（TNF）信號通路及蛋白激酶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）等核心靶點發(fā)揮治療濕疹的作用。分子對接進一步驗證主要成分和關鍵靶點的相互作用，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MMP9、AKT1的對接親和度較高。結論 網(wǎng)絡藥理學聯(lián)用分子對接技術揭示蛇床子可以通過多成分、多靶點、多途徑改善濕疹，為其進一步深入研究及臨床應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

國家自然科學基金資助項目（82104312）；中央高?；究蒲袠I(yè)務費專項資金資助項目（2042022kf1077）