基于网络药理学探析参桃软肝丸治疗肝细胞癌的机制＊

目的 利用网络药理学探析参桃软肝丸治疗肝细胞癌（hepatocellular carcinoma,HCC）的机制。方法 从中药系统药理学分析平台收集组方药物的活性成分及靶点,与Genecards网站收集的HCC靶点取交集后,筛选出参桃软肝丸治疗HCC的潜在靶点,进而绘制中药-活性成分-靶点网络图并分析其关键成分,构建靶蛋白互作网络并分析其关键靶点,并进行基因本体分子功能和京都基因与基因组百科全书通路富集分析,最后通过分子对接探讨关键成分与关键靶点的相互作用。结果 参桃软肝丸治疗HCC的关键成分或为槲皮素、木犀草素、山奈酚,关键靶点或为蛋白激酶B、半胱氨酸天冬氨酸蛋白酶3、血管内皮生长因子A、V-Jun肉瘤病毒癌基因同源物、V-MYC骨髓细胞瘤病毒癌基因同源物,其作用机制或与乙型肝炎、丙型肝炎、磷脂酰肌醇3激酶/蛋白激酶B信号通路、p53信号通路、癌症中微小RNA、细胞程序性死亡配体1表达和细胞程序性死亡蛋白1检查点途径、细胞凋亡、低氧诱导因子-1信号通路、白介素-17信号通路、叉头框转录因子O信号通路有关。分子对接表明AKT1蛋白与木犀草素结合能力最强。结论 本文表明参桃软肝丸治疗HCC多靶点、多通路的作用机制,可为今后阐明参桃软肝丸治疗HCC的具体机制提供思路。

Mechanism of Shentao Ruangan Pill for Hepatocellular Carcinoma Based on Network Pharmacology

Objective To explore the pharmacological mechanism of hepatocellular carcinoma treatment with Shentao Ruangan Pill based on network pharmacology.Methods Both active ingredients and targets of Shentao Ruangan Pill were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the HCC targets collected from the Genecards website were mapped to potential targets of Shentao Ruangan Pill for the treatment of HCC. The herb-active ingredient-target network was built and analyzed for key ingredients and the protein-protein interaction network was constructed and studied for key targets. Furthermore, Gene Ontology analysis (GO) of molecular function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Finally, relations between key ingredients and key genes were investigated by the method of molecular docking.Results Key ingredients of Shentao Ruangan Pill for HCC may be quercetin, luteolin and kaempferol while key therapeutic targets may be protein kinase B(PKB or AKT1), caspase-3(CASP3), vascular endothelial growth factor A(VEGFA) , V-Jun sarcoma virus 17 oncogene homolog(JUN), V-Myc Myelocytomatosis Viral Oncogene Homolog(MYC). The therapeutic mechanism may be related to hepatitis B, hepatitis C, phosphatidylinositol 3-kinase/protein kinase B (PI3K/PKB or PI3K/Akt) signaling pathway, p53 signaling pathway, microRNAs in cancer, programmed cell death ligand 1 (PD-L1) expression and programmed cell death protein1(PD-1) checkpoint pathway in cancer, apoptosis, hypoxia inducible factor-1(HIF-1) signaling pathway, interleukin-17(IL-17) signaling pathway and Forkhead box O (FoxO) signaling pathway. Molecular docking reveals a reliable interaction between AKT1 and quercetin, kaempferol as well as luteolin.Conclusion The study indicates that mechanisms of Shentao Ruangan Pill for HCC are likely to involve multi-target and multi-pathway, which could provide ideas for clarifying the specific mechanism of HCC treatment with Shentao Ruangan Pill in the future.