八角莲化学成分及其抗癌活性的网络药理学研究

Study on the chemical constituents and anticancer mechanisms of Dysosma versipellis by network pharmacology

目的研究八角莲Dysosma versipellis根茎的化学成分,并采用网络药理学方法对其抗癌活性进行分析。方法运用硅胶柱层析色谱、凝胶色谱、ODS柱色谱等分离技术,现代波谱技术(NMR、MS、IR、UV)对八角莲的化学成分进行分离纯化及结构鉴定,采用GO、KEGG等方法对分离所得的化学成分可能的作用靶点、通路等信息进行富集分析。结果分离得到了14个化合物,鉴定为:苦鬼臼脂毒酮(1)、异苦鬼臼酮(2)、苦鬼臼素-4-O-β-D-葡萄糖苷(3)、鬼臼毒酮(4)、苦鬼臼毒素-4-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷(5)、苦鬼臼毒素(6)、4′-去甲基去氢鬼臼毒素(7)、4′-去甲去氧鬼臼毒素(8)、4′-去甲基鬼臼毒酮(9)、山荷叶素(10)、4′-去甲基鬼臼毒素(11)、山荷叶-4-O-β-D-葡萄糖苷(12)、鬼臼毒素-4-O-β-D-葡萄糖苷(13)、去氢鬼臼毒素(14)。网络药理学研究结果表明上述成分可能通过对激素响应、跨膜受体蛋白酪氨酸激酶信号通路、胰岛素样生长因子受体信号通路等生物学过程,作用于AKT1、EGFR、HSP90AA1、MAPK3、MTOR等关键靶点,癌症通路、前列腺癌通路、脂质与动脉粥样硬化通路等发挥抗癌活性。结论其中化合物1、2、5、7~9和14为首次从八角莲中分离得到;八角莲中的多种成分可以通过多个靶点、多个通路发挥抗癌作用。

Objective To study the chemical constituents and anticancer activity of Dysosma versipellis(D.versipellis)by network pharmacology method.Methods Silica gel column chromatography,Sephadex LH-20 chromatography,high-performance liquid chromatography,and modern spectral techniques(NMR,MS,IR,UV)were used to identify the structures of compounds isolated from the ethyl acetate fraction of D.versipellis.GO,KEGG and other methods were used to enrich and analyze the targets,pathways and other information of the isolated chemical components.Results Fourteen compounds were isolated from D.versipellis and identified as Picropodophyllotoxon(1),Isopicropodophyllone(2),Picropodophyllotoxin-4-O-β-D-glucoside(3),Podophyllotoxone(4),Picropodophyllotoxin-4-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside(5),Picropodophyllin(6),4′-Demethyldehydropodophyllotoxin(7),4′-Demethyldesoxypodophyllotoxin(8),4′-Demethylpodophyllotoxone(9),Diphyllin(10),4′-Demethylpodophyllotoxin(11),Diphyllin-4-O-β-D-glucoside(12),Podophyllotoxin-4-O-β-D-glucoside(13),Dehydropodophyllotoxin(14).Compounds 1-3 were isolated from D.versipellis for the first time.The above components may act on AKT1,EGFR,HSP90AA1,MAPK3,MTOR and other key targets through biological processes such as hormone response,transmembrane receptor protein tyrosine kinase signaling pathway,insulin-like growth factor receptor signaling pathway,cancer pathway,prostate cancer pathway,lipid and atherosclerosis pathway.Conclusion Compounds 1,2,5,7-9 and 14 were isolated from this plant for the first time.A variety of components in D.versipellis could exert anticancer effects through multiple targets,multiple pathways,and multiple levels.