基于网络药理学的白屈菜抗肿瘤分子机制研究

目的白屈菜临床用于肿瘤治疗,具有良好的疗效,且毒副作用小。运用网络药理学方法筛选白屈菜有效部位和主要活性成分,构建活性化合物-靶点网络,对其抗肿瘤作用的分子机制进行科学阐释。方法采用ADME计算方法筛选白屈菜活性成分,通过文献挖掘、多个数据库联用检索收集白屈菜活性成分与潜在靶点,并利用Sys DT模型对化合物靶点进行筛选。利用Cytoscape软件构建化合物-靶点网络并进行网络拓扑学分析,通过生物学信息注释数据库(DAVID)分析靶点基因功能及信号通路。结果生物碱是白屈菜抗肿瘤主要活性成分,通过ADME方法筛选出21种生物碱类成分,相关靶点168个,肿瘤相关通路60条,整合相关通路绘制了白屈菜抗肿瘤通路。根据网络拓扑学分析结果以及成分修正结果推测,白屈菜红碱、小檗碱和血根碱为白屈菜主要活性成分,作用于PTGS2、SCN5A、F10、NCOA2、CHRM3、AR、TP53、CASP1/3/9、DRD1、MAPT、MAPK1和BLM等关键靶点。结论白屈菜主要通过诱导细胞凋亡和抑制细胞增殖、转移和侵袭等多表型干预的网络模式产生作用,从而发挥抗肿瘤活性,且具有一定的中枢镇痛作用。

Study on antitumor molecular mechanism of Chelidonium majus based on network pharmacology

Objective Chelidonium majus is applied to tumor therapy with good clinical effect and weak adverse effect. To explain the molecular mechanism of antitumor effect scientifically, the network pharmacology method was used to screen effective parts and major active components of C. majus and to construct the active compounds-targets network.Methods ADME calculation method was used to filtrate the active components of C. majus, and then the targets of the main active ingredients were collected by literature mining and multiple databases, and the targets of the compound were screened using the SysDT model. Besides, the compounds-targets network was constructed by Cytoscape software and network topology analysis was carried out. Biological information annotation databases (DAVID) was used to analyze the molecular function and biological pathway of the action targets.Results Alkaloids were the major active components of C. majus, 21 alkaloid components were screened out by ADME calculation method with 168 related targets, and 60 closely cancer-related pathways. Those pathways were integrated, with which a comprehensive C. majus antitumor pathway was constructed. According to the results of network topology analysis and ingredient correction results, it was speculated that chelerythrine, berberine and sanguinarine were the main active ingredients in C. majus, acting on the targets of PTGS2, SCN5A, F10, NCOA2, CHRM3, AR, TP5, CASP1/3/9, DRD1, MAPT, MAPK1, BLM, etc.Conclusion The antitumor activities of C. majus were mainly by inducing cell apoptosis and inhibiting cell proliferation, metastasis and invasion as phenotype intervention mode in network, thereby to exert antitumor activities and a certain central analgesic effect.