目的 探討黃精抗腫瘤的藥效物質(zhì)基礎(chǔ)及分子作用機(jī)制。方法 采用中藥網(wǎng)絡(luò)藥理學(xué)數(shù)據(jù)庫(kù)和分析平臺(tái)（TCMSP）對(duì)黃精的化學(xué)成分進(jìn)行收集，借助計(jì)算機(jī)輔助預(yù)測(cè)吸收、分布、代謝和排泄（ADME）性質(zhì)并結(jié)合obioavail 1.1和pre-Caco-2預(yù)測(cè)模型對(duì)活性成分群進(jìn)行初篩；對(duì)所有潛在活性成分進(jìn)行靶點(diǎn)識(shí)別；采用Cytoscape3.6.1軟件進(jìn)行“活性成分-靶標(biāo)”網(wǎng)絡(luò)的構(gòu)建，并利用“network analyzer”插件對(duì)網(wǎng)絡(luò)的拓?fù)湫再|(zhì)進(jìn)行分析；采用在線分析工具DAVID進(jìn)行KEGG通路富集分析。結(jié)果 黃精中已鑒定的39個(gè)化合物，其中18個(gè)具有良好的ADME性質(zhì)的化合物，這些潛在的活性成分中，共有14個(gè)活性成分及其對(duì)應(yīng)的19靶標(biāo)與黃精抗腫瘤的活性密切相關(guān)。通過(guò)構(gòu)建“活性成分-靶點(diǎn)”網(wǎng)絡(luò)及對(duì)網(wǎng)絡(luò)進(jìn)行分析，共獲得個(gè)4關(guān)鍵化合物：黃芩素、3’-甲氧基大豆苷元、異甘草素、（2R）-7-羥基-2-（4-羥苯基）-4-苯丙二氫呋喃；2個(gè)關(guān)鍵靶標(biāo)：前列腺素G/H合酶2、熱休克蛋白90AA1。在對(duì)靶點(diǎn)進(jìn)行KEGG通路分析時(shí)，共獲得12條與抗腫瘤相關(guān)的通路。結(jié)論 黃精可通過(guò)多成分、多靶點(diǎn)及多通路的作用機(jī)制發(fā)揮其抗腫瘤活性。

Objective To investigate the pharmacodynamic substance basis and molecular mechanism of Polygonatum sibiricum against tumor diseases. Methods The chemical components of Rhizoma Polygonatum were collected by TCMSP platform, and the properties of ADME were predicted with the aid of computer, and obioavail 1.1 1.1 and pre-caco-2 prediction models are used to screen the active ingredient group. Identify the target of all potential active ingredients, build the "active ingredient target" network by using the software of Cytoscape 3.6.1, analyze the topological properties of the network by using the plug-in of "network analyzer", and analyze the enrichment of KEGG pathway by using the online analysis tool David. Results 39 compounds identified in Polygonatum sibiricum, 18 of them have good ADME properties. Among these potential active ingredients, a total of 14 active ingredients and their corresponding 19 targets are closely related to the anti-tumor disease activity of Polygonatum sibiricum. Four key compounds, including baicalein, 3 ' - methoxydaidzein, isoliquiritigenin, (2R) - 7-hydroxy-2 - (4-hydroxyphenyl) - 4-phenylpropyldihydrofuran; and two key targets including prostaglandin G/H synthase 2 and Heat shock protein HSP 90 were obtained by constructing and analyzing the "active component-target" network. In addition, a total of 12 pathways related to antitumor disease were obtained when the KEGG pathway analysis was performed on the target. Conclusion Polygonatum sibiricum can exert its anti-tumor disease activity through the action mechanism of multiple components, multiple targets and multiple pathways.

R965

陜西省重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2018SF-327）