[關(guān)鍵詞]
[摘要]
目的 采用網(wǎng)絡(luò)藥理學(xué)方法探究干姜的主要活性成分及其抗癌作用機制。方法 在中藥系統(tǒng)藥理學(xué)分析平臺(TCMSP)數(shù)據(jù)庫中檢索干姜的化學(xué)成分,根據(jù)"類藥五原則"與"口服生物利用度"≥ 30%這一標準篩選干姜的活性成分,預(yù)測其活性成分對應(yīng)的作用靶點,采用Cytoscape 3.2.1軟件構(gòu)建活性成分-預(yù)測靶點網(wǎng)絡(luò)圖。在Genecards數(shù)據(jù)庫中以"anti-cancer "為關(guān)鍵詞搜索抗癌靶點,與干姜靶點映射篩選出共同靶點作為干姜的抗癌靶點。將干姜抗癌靶點導(dǎo)入STRING數(shù)據(jù)庫中進行蛋白質(zhì)-蛋白質(zhì)相互作用分析,構(gòu)建靶蛋白相互作用網(wǎng)絡(luò)圖(PPI),利用Cytoscape3.2.1的"CytoNCA"插件篩選干姜的抗癌核心靶點。使用DAVID數(shù)據(jù)庫及Cytoscape3.2.1的"GlueGO"插件對干姜抗癌靶點進行KEGG信號通路富集分析和GO生物過程富集分析,并構(gòu)建干姜活性成分-核心抗癌靶點-信號通路網(wǎng)絡(luò)圖。結(jié)果 獲得干姜中具有類藥性、口服吸收良好的活性成分52種,對應(yīng)靶點101個。其中抗癌靶點39個,核心靶點10個。KEGG富集分析得到與干姜抗癌作用有關(guān)的信號通路68條,主要涉及腫瘤壞死因子(TNF)信號通路、血管內(nèi)皮生長因子(VEGF)信號通路等。GO富集分析得出與干姜抗癌作用有關(guān)的生物過程35個,主要涉及到一氧化氮生物合成、細胞增殖與凋亡等。結(jié)論 本研究初步揭示了干姜的藥效物質(zhì)基礎(chǔ)及其可能的抗癌作用機制,為干姜抗癌研究提供參考。
[Key word]
[Abstract]
Objective To explore the active components and the anti-cancer mechanism of Zingiberis Rhizoma by network pharmacology. Methods The components of Zingiberis Rhizoma were searched through the Chinese Medicine System Pharmacology (TCMSP) database. The active components of Zingiberis Rhizoma were screened with "Lipinski rule" and "Oral Bioavailability ≥ 30%" rules, the corresponding targets of the active components were predicted. Cytoscape 3.2.1 was used to build a network between components and targets. Anti-cancer targets were searched from Genecards database with the keyword "anticancer", the anti-cancer targets was mapped to the targets of Zingiberis Rhizoma to screen out the common targets as the anti-cancer targets of Zingiberis Rhizoma. The anti-cancer targets of Zingiberis Rhizoma were imported into STRING database for proteinprotein interaction analysis, and the target protein interaction network graph (PPI) was constructed. Cytoscape 3.2.1 "CytoNCA" plug-in unit was used to screen the key anti-cancer targets of Zingiberis Rhizoma. DAVID database and Cytoscape 3.2.1 "ClueGO" plug-in unit were used to perform KEGG pathway enrichment analysis and GO biological process enrichment analysis, and build active ingredients-key anticancer targets-KEGG pathway network map. Results 52 components and 101 corresponding targets of Zingiberis Rhizoma with drug-like properties and good oral absorption were obtained. Among them, there were 39 targets with anticancer effects and 10 key anti-cancer targets. KEGG signaling pathway analysis of anti-cancer targets of Zingiberis Rhizoma obtained 68 signaling pathways, mainly related to TNF signaling pathway and VEGF signaling pathway, etc. GO biological process analysis obtained 35 biological processes, mainly involved in nitric oxide biosynthesis, cell proliferation and apoptosis, etc. Conclusion This study preliminarily revealed the pharmacodynamic substance basis of Zingiberis Rhizoma and its possible anticancer pharmacological effects, providing basis for anti-cancer research of Zingiberis Rhizoma.
[中圖分類號]
[基金項目]
河南省自然科學(xué)基金資助項目(182300410310);鄭州工業(yè)應(yīng)用技術(shù)學(xué)院校級科研項目(2018YB021)