基于网络药理学和分子对接技术探究知柏地黄汤治疗膀胱癌的作用机制

Study of molecular mechanisms of ZhibaiDihuang Decoction in treatment of bladder cancer based on network pharmacology and molecular docking method

通过建立“组分-靶点-生物学通路”,探寻知柏地黄汤主要活性成分治疗膀胱癌的物质基础.建立知柏地黄汤组分库,借助TCMSP数据库获得中药作用靶点.基于GeneCards数据库检索与膀胱癌相关靶点并与中药靶点映射得到关键靶点,通过STRING平台构建关键靶点互作网络.采用Cytoscape 3.7.2软件识别Hub靶点,借助DAVID 6.8数据库探寻组分抗膀胱癌的关键通路并对关键靶点进行GO富集分析,采用Schr?dinger进行Hub靶点与知柏地黄汤组分的分子对接验证.获得包括VEGFA,FOS,MYC,CASP3,CCND1,HIF1A在内的Hub靶点9个,映射GO结果759条,集中在生物过程.映射KEGG通路56条,如PI3K-Akt信号通路、MAPK信号通路、p53信号通路等.分子对接筛选出毛蕊花糖苷、梓醇、知母皂苷BII等先导化合物.知柏地黄汤治疗膀胱癌的潜在机制可能与参与抗炎、调节糖脂代谢及氧化应激等过程有关,为阐明知柏地黄汤对膀胱癌的作用机制提供了科学依据.

The “ingerdient-targrt-pathway” was constructed to explore the material basis of ZhibaiDihuang Decoction in the treatment of bladder cancer.The compound database of ZhibaiDihuang Decoction was established and the targets of these compounds were obtained from TCMSP.The bladder cancer-related targets were screened from GeneCardsdatabase and mapped with traditional Chinese medicine targets to obtain key targets.The key targets interaction network was built by string database.Hub targets were identified by the software Cytoscape 3.7.2,and DAVID database 6.8 was used to explore the key pathways of anti-bladder cancer and GO enrichment analysis.The molecular docking between Hub target and ZhibaiDihuang Decoction was verified by Schr?dinger.Nine hub targets were obtained, including VEGFA,FOS,MYC,CASP3,CCND1 and HIF1 A.759 GO pathwayswere mapped, mainly in the biological processes.56 KEGG pathways were mapped, such as PI3 K-Akt signaling pathway, MAPK signaling pathway, p53 signaling pathway, etc.The lead compounds such as calyx glycoside, catalpol and anemarrhenoside BII were screened by molecular docking.The investigation indicated that the potential mechanism of this prescriptionmight be mainly involved in the process of anti-inflammatory, regulating glucose and lipid metabolism and oxidative stress, which provided a scientific basis for elucidating the mechanism of ZhibaiDihuang Decoction on bladder cancer.