基于网络药理学探讨威灵仙-天花粉药对抗癌的作用机制

Anti-cancer Mechanism of "Clematis Radix et Rhizoma-Trichosanthis Radix" Based on Network Pharmacology

目的:基于网络药理学探讨"威灵仙-天花粉"抗癌症的潜在靶点和作用机制。方法:应用中药系统药理学分析平台(TCMSP)根据口服生物利用度(OB)和类药性(DL)对威灵仙和天花粉的活性成分和相应靶蛋白进行筛选;应用GeneCards,OMIM数据库筛选癌症疾病的靶点,应用R语言软件筛选威灵仙、天花粉与癌症疾病共同靶点;应用Cytoscape3.7.2软件构建"药物-活性成分-疾病-靶点"网络图;应用STRING数据库绘制共同靶点蛋白互作网络(PPI);应用R语言软件对有效作用靶点进行基因本体(GO)功能,京都基因与基因组百科全书(KEGG)通路富集分析。结果:从威灵仙-天花粉药对中共获得9个有效活性成分,共检索出31个靶点基因,从癌症疾病中检索出的相关靶基因为814个,两者相关靶基因进行匹配,得到共同靶基因9个,这些靶点主要涉及内肽酶、半胱氨酸型内肽酶活性参与凋亡过程以及癌症坏死因子受体超家族结合等生物学过程,并通过调节细胞凋亡,麻疹,乙型肝炎,卡波西肉瘤相关疱疹病毒感染,p53,白细胞介素(IL)-17,肿瘤坏死因子(TNF)等多条通路从而发挥治疗癌症的作用。结论:初步研究了威灵仙-天花粉治疗癌症的作用机制,威灵仙-天花粉药对具有多个活性成分,能通过多个靶点、多个通路来发挥治疗癌症的作用。

Objective: To explore the potential targets and mechanism of action of "Clematis Radix et Rhizoma-Trichosanthis Radix" based on network pharmacology. Method: Chinese Medicine System Pharmacology Analysis Platform(TCMSP)was used to screen out active ingredients and corresponding target proteins of Clematis Radix et Rhizoma and Trichosanthis Radix according to oral bioavailability(OB)and drug likeness(DL),cancer disease targets were screened out using GeneCards and OMIM databases,R language software was used to screen out common targets of clematis,trichosanthin and cancer diseases,Cytoscape 3.7.2 software was used to construct a network map of "drug-active ingredient-disease-target",STRING database was used to draw protein protein interaction(PPI)of common target proteins,R language software was used to perform enrichment analysis of gene ontology(GO)functions and Kyoto encyclopedia of genes and genomes(KEGG)channels on effective targets. Result: A total of 9 effective active ingredients were obtained from Clematis Radix et Rhizoma-Trichosanthis Radix powder pair. A total of 31 target genes were searched,and 814 relevant target genes were searched from cancer diseases. The two kinds of relevant target genes were matched to obtain 9 common target genes,which mainly involved endopeptidase,cysteine-type endopeptidase activities involving in the apoptosis process and cancer necrosis factor receptor superfamily binding and other biological processes,and played a role in the treatment of cancers by regulating apoptosis,measles,hepatitis B,kaposi sarcoma-associated herpesvirus infection,p53,interleukin-17(IL-17),tumor necrosis factor(TNF)and many other pathways. Conclusion: The mechanism of Clematis Radix et Rhizoma-Trichosanthis Radix in the treatment of cancer is preliminarily studied. Clematis Radix et Rhizoma-Trichosanthis Radix has multiple active ingredients and can play a role in treating cancer through multiple targets and multiple pathways.