党参、白花蛇舌草防治结直肠癌术后复发转移的网络药理学研究

Network pharmacological study of Codonopsis Radix and Hedyotis Diffusae Herba in prevention and treatment of recurrence and metastasis of postoperative colorectal cancer

目的本研究通过网络药理学预测并筛选党参、白花蛇舌草治疗结直肠癌的活性成分及其潜在作用靶点,探讨党参、白花蛇舌草防治结直肠癌术后复发转移的相关作用机制。方法运用中药系统药理学分析平台(TCMSP),以口服利用度(OB)≥30%、类药性(DL)≥0.18为参数筛选候选化合物成分,并预测其潜在靶点;通过Uniprot数据库检索药物靶点对应的人类基因,在Genecard数据库中检索结直肠癌对应的基因,采用String工具对药物和疾病基因进行蛋白互作网络(PPI)分析,绘制疾病靶点PPI,构建药物成分-靶点基因-疾病关系网络,合并网络筛选核心基因,分别行GO功能、KEGG通路富集分析。结果从党参、白花蛇舌草中共得到28个候选化合物,所对应的靶点共469个,药物靶点对应的人类基因排除未找到的共196个,结直肠癌对应的基因8248个,药物基因与疾病基因中心交集63个,构建的成分-靶点-疾病关系网络中共63个节点,569个连接。GO功能分析提示,相关作用机制涉及分子功能、细胞组成和生物过程3个方面,发现结直肠癌可能与调控平滑肌和上皮细胞的增殖、调控DNA结合转录因子活性、血液循环以及对营养水平的反应等有关。基因KEGG通路富集分析提示,结直肠癌的发病机制可能与p53信号通路和PI3K/Akt信号通路有关。结论党参、白花蛇舌草防治结直肠癌术后复发转移的作用机制可能与其有效成分干预p53信号通路和PI3K/Akt信号通路等有关,为阐明其治疗结直肠癌术后患者的潜在作用机制提供了新的方向。

Objective To predict and screen the active components and potential targets of Codonopsis Radix and Hedyotis Diffusae Herba in treatment of colorectal cancer by means of network pharmacology,and to investigate the mechanism of Codonopsis Radix and Hedyotis Diffusae Herba in the prevention and treatment for recurrence and metastasis of postoperative colorectal cancer.Methods The candidate components and potential targets of Codonopsis Radix and Hedyotis Diffusae Herba were screened out by traditional Chinese medicine systematic pharmacological(TCMSP)database,with oral bioavilability(OB)≥30%and drug-like(DL)≥18%as the parameters.The human genes corresponding to the medicine target sites were obtained from Uniprot database,and the genes corresponding to colorectal cancer from Genecard database.String tool was applied to build the disease-gene target protein-protein interaction(PPI)network,and then construct the component-target-disease network.Cytoscape software was used to merge the networks,and the core network for gene were screened out for GO function analysis and KEGG pathway enrichment analysis.Results A total of 28 active components were screened out from Codonopsis Radix and Hedyotis Diffusae Herba,and their corresponding targets were 469.A total of 196 human genes were obtained corresponding to the medicine target sites,as well as 8248 genes corresponding to colorectal cancer,63 intersections of drug gene and disease gene,63 nodes and 569 connections in the component-target-disease network.Gene GO function analysis suggested that the related mechanism involved molecular functions,cell components and biological process,and that colorectal cancer might be related to the regulation of proliferation of smooth muscle and epithelial cell,DNA binding transcription factor activity,blood circulation and response to nutrient levels,etc.Gene KEGG pathway enrichment analysis showed that the mechanism of colorectal cancer might be associated with P53 signaling pathway and PI3K/Akt signaling pathway.Conclusion The possible mechanism of Codonopsis Radix and Hedyotis Diffusae Herba in treating postoperative colorectal cancer may be related to the intervention of P53 signaling pathway and PI3K/Akt signaling pathway by their active components.This study provides a new direction for further study on the potential mechanism of Codonopsis Radix and Hedyotis Diffusae Herba in treating postoperative colorectal cancer.