目的 基于網(wǎng)絡(luò)藥理學方法和分子對接技術(shù)探究冬蟲夏草抗腫瘤的作用機制。方法 利用TCMSP、CNKI、PubMed、Drugbank、Stitch和Swiss target prediction等平臺檢索冬蟲夏草的化學成分和作用靶點;通過GeneCards、OMIM等數(shù)據(jù)庫篩選腫瘤相關(guān)基因,運用Cytoscape 3.7.2構(gòu)建冬蟲夏草活性成分-靶點網(wǎng)絡(luò),通過String數(shù)據(jù)庫對關(guān)鍵靶點構(gòu)建網(wǎng)絡(luò)互作(PPI)網(wǎng)絡(luò),并進行基因本體(GO)基因和京都基因和基因組百科全書(KEGG)通路富集分析,最后利用AutoDock Vina軟件和Pymol軟件對藥物有效活性成分和關(guān)鍵靶點進行分子對接驗證。結(jié)果 共得到冬蟲夏草22個化合物,86個抗腫瘤共同靶點,主要包括環(huán)加氧酶(PTGS)2、絲裂原活化蛋白激酶3(MAPK3)、過氧化物酶體增生激活受體γ(PPARG)、胱天蛋白酶3(CASP3)、JUN基因等關(guān)鍵靶點。GO分析與KEGG通路結(jié)果顯示,冬蟲夏草抗腫瘤涉及到多種生物學過程以及PPAR、花生四烯代謝、5-羥色胺信號通路等多種信號通路。將關(guān)鍵化合物和靶點進行分子對接,提示冬蟲夏草抗腫瘤可能的前5個主要活性成分11,14-二十碳二烯酸、花生四烯酸、黃豆黃素、膽甾醇和豆甾醇與關(guān)鍵靶點PTGS2、PTGS1、PGR、HMGCR和CNR1均能自發(fā)結(jié)合。結(jié)論 初步探討了冬蟲夏草抗腫瘤的主要活性成分、相關(guān)靶點及相關(guān)通路,發(fā)現(xiàn)冬蟲夏草可以通過多成分、多靶點、多通路抗腫瘤,為后期實驗驗證提供了參考依據(jù)。

Objective To investigate the anti-tumor mechanism of Cordyceps sinensis based on network pharmacological methods and molecular docking. Methods The chemical composition and action targets of Cordyceps sinensis were retrieved by TCMSP, CNKI, PubMed, Drugbank, Stitch, and Swiss target prediction platforms, tumor-related genes were screened by GeneCards, OMIM and other databases, Cytoscape 3.7.2 was used to construct Cordyceps sinensis active ingredient and target network, and PPI network was constructed from String database for key targets. GO function and KEGG pathway enrichment analysis were carried out, and finally AutoDock Vina software and Pymol software were used to verify the molecular docking of the active ingredients and key targets of the drug. Results A total of 22 compounds and 86 anti-tumor common targets of Cordyceps sinensis were obtained through screening, including key targets such as PTGS2, MAPK3, PPARG, CASP3, and JUN. GO analysis and KEGG pathway results showed that Cordyceps sinensis anti-tumor involves a variety of biological processes as well as a variety of signaling pathways such as PPAR, arachidonic metabolism, serotonin signaling pathway. The key compounds and the target were docking, suggesting that the top five possible anti-tumor components, 11, 14-eicosadienoic acid, arachidonic acid, soybean flavin, cholesterol, and stigmasterol, could spontaneously bind to the key targets, PTGS2, PTGS1, PGR, HMGCR and CNR1. Conclusion In this paper, the main active ingredients, related targets and related pathways of Cordyceps sinensis anti-tumor are preliminarily discussed, and it is found that Cordyceps sinensis can resist tumors through multi-component, multi-target and multi-pathway, which provides a reference basis for later experimental verification.

R285.5

深圳市“醫(yī)療衛(wèi)生三名工程”項目（SZZYSM202106004）