“温升三阴,肃金秘阳法”抗肝癌的网络药理学研究

The Network Pharmacological Study on the Treatment of Hepatocellular Carcinoma with the Warming and Ascending Three Yin,Descending Metal and Storing Yang Law

目的通过对“温升三阴,肃金秘阳法”的网络药理学分析,探讨此治法在治疗肝细胞癌的潜在抗肿瘤靶点及作用机制,为后续实验研究提供有针对性的指导。方法利用TCMSP数据库对“温升三阴,肃金秘阳法”下对应中药所含化学成分进行筛选并预测其作用靶点。通过Gene Cards数据库、OMIM数据库获得肝细胞癌的相关靶点,然后利用Cytoscape 3.7.2软件构建药物-疾病-靶标关系网络。利用R语言,获得两者的交集靶点蛋白并通过STRING平台进行蛋白质互作网络分析。对关键靶点及相关有效化学成分做分子对接验证。利用DIVID数据库进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果“温升三阴,肃金秘阳法”治疗肝细胞癌的关键成分涉及到槲皮素、β-谷甾醇、山柰酚、豆甾醇;关键靶基因主要有PTGS2、STAT3、HSP90AA1、AKT1等,主要生物学过程有信号转导、氧化还原过程、药物反应、凋亡过程、炎症反应等;作用机制与PI3K/Akt信号通路、TNF信号通路、乙型肝炎信号通路、MAPK信号通路有关。结论“温升三阴,肃金秘阳法”对肝细胞癌的治疗作用可能是多靶点、多途径、多层次的,并且可以推测槲皮素和山柰酚可能是其中比较重要的2个有效成分。PTGS2、STAT3、AKT可能是主要的作用靶点。PI3K/Akt信号通路、TNF信号通路可能是本方发挥作用比较重要的两条信号通路。

Objective Through network pharmacology,the“the warming and ascending three Yin,descending metal and storing Yang law”(温升三阴,肃金秘阳法),was analyzed to explore the potential anti-tumor target and mechanism in the treatment of hepatocellular carcinoma,so as to provide targeted guidance for the follow-up research.Methods The TCMSP database was used to screen the chemical components contained in the corresponding traditional Chinese medicine under the method of“the warming and ascending three Yin,descending metal and storing Yang law”and to predict their action targets.The relevant targets of hepatocellular carcinoma were obtained through Gene Cards database and OMIM database.Cytoscape 3.7.2 software was used to construct drug-disease-target relationship network.R language was used to obtain the intersection target protein of the two.Protein-protein interaction network analysis was carried out on the STRING platform,and Molecular docking verification of key targets and related active chemical components was performed.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DIVID database.Results The key components in the treatment of primary liver cancer were quercetin,β-sitosterol,kaempferol and stigmasterol.The key target genes mainly included PTGS2,STAT3,HSP90Aa1 and AKT1.In this method,the main biological processes may be signal transduction,redox process,drug reaction,apoptosis,inflammation and so on.The mechanism of action may be related to PI3K/Akt signaling pathway,TNF signaling pathway,hepatitis B signaling pathway and MAPK signaling pathway.Conclusion The therapeutic effect of“the warming and ascending three Yin,descending metal and storing Yang law”on hepatocellular carcinoma may be multi-target,multi-pathway and multi-level.It can be speculated that quercetin and kaempferol may be the two more important active components.PTGS2,STAT3,and AKT may be the main targets,and PI3K/Akt signaling pathway,TNF signaling pathway may be the two more important signaling pathways that this method plays a role in.