基于网络药理学和分子对接探究余甘子治疗肝细胞癌的分子机制

目的:基于网络药理学及分子对接虚拟预测方法,探究余甘子治疗肝细胞癌的潜在分子机制。方法:通过公共数据库获取余甘子的有效活性成分及作用靶点,并筛选肝细胞癌相关靶点,构建“活性成分-靶点”关系图与PPI网络,进行GO分析和KEGG、Reactome通路富集,采用分子对接评价活性成分与核心靶点的结合活性。结果:共获得19个有效活性成分和12个重要靶点。通过GO分析获得了1794个细胞生物过程,而KEGG和Reactome富集分析分别涉及315和391个相关通路。结论:余甘子的主要有效活性成分为鞣花酸、木犀草素、槲皮素和山奈酚,可能作用于AKT1、MMP9、SRC、ESR1、PPARG和AR等关键靶点,调控内分泌抵抗、癌症中的蛋白多糖、癌症通路、受体酪氨酸激酶信号、白细胞介素信号通路、生长因子受体和第二信使信号转导、PI3K/AKT信号通路等以治疗肝癌。除了直接的肿瘤相关信号通路,间接的炎症、代谢通路在抑制肝癌进展中发挥了重要作用。

Network pharmacology and molecular docking-based research on molecular mechanism of Phyllanthus emblica in the treatment of hepatocellular carcinoma

Objective:To explore the potential molecular mechanism of Phyllanthus emblica in the treatment of hepatocellular carcinoma based on network pharmacology and molecular docking virtual prediction methods.Methods:Firstly,we screened active components of Phyllanthus emblica and their targets,as well as hepatocellular carcinoma-related targets via public databases.Then,the“Component-Target”network and the PPI network were constructed,and enrichment analyses were made on GO biological process,KEGG pathway,and Reactome pathway to uncover the key signal pathway.Finally,molecular docking was used to evaluate the binding activity of the active components to the key targets.Results:A total of 19 active components and 12 pivotal targets were selected.1794 cellular biological processes were acquired through GO biological process analysis,while KEGG enrichment analysis and Reactome pathway analysis involved 315 and 391 related pathways respectively.Conclusion:The main active components of Phyllanthus emblica are ellagic acid,luteolin,quercetin,and kaempferol.They may act on key targets such as AKT1,MMP9,SRC,ESR1,PPARG,and AR.Furthermore,to treat hepatocellular carcinoma,Phyllanthus emblica could regulate endocrine resistance,proteoglycans in cancer,pathways in cancer,signaling by receptor tyrosine kinases,signaling by interleukins,diseases of signal transduction by growth factor receptors and second messengers,and PI3K/AKT signaling in cancer.In addition to direct tumor-related signaling pathways,many indirect pathways involving inflammation and metabolism inhibit the development of hepatocellular carcinoma.