MO Jiahao,XU Hongbin,LI Jing,et al.Discussion on Mechanism of Zuojin Pills in Treatment of Hepatocellular Carcinoma Based on Network Pharmacology[J].zhongguo zhongyiyao xinxi zazhi,2021,28(2):19-27.[doi:10.19879/j.cnki.1005-5304.202001256]
基于网络药理学的左金丸治疗肝癌机制探讨
- Title:
- Discussion on Mechanism of Zuojin Pills in Treatment of Hepatocellular Carcinoma Based on Network Pharmacology
- 文章编号:
- 1005-5304(2021)02-0019-09
- Keywords:
- Zuojin Pills; hepatocellular carcinoma; network pharmacology; pathway
- 分类号:
- R273.57；R285.5
- 文献标志码:
- A
- 摘要:
- 目的 运用网络药理学研究左金丸治疗原发性肝癌的作用机制。方法 通过中药系统药理学数据库与分析平台（TCMSP）获取左金丸的化合物及靶点，以口服生物利用度（OB）≥30%和类药性（DL）≥0.18为阈值进行化合物筛选，将靶点输入Uniprot获取靶点对应的基因Symbol；从人类基因数据库（GeneCards：The Human Gene Database）获取原发性肝癌的疾病基因，并筛选出与左金丸靶点基因的交集基因；运用Cytoscape3.7.1软件绘制活性成分-靶点、疾病-中药-化合物-交集靶点（基因）网络图；运用String构建蛋白相互作用网络，运用g:Profiler数据分析平台进行GO富集及KEGG通路富集分析；联合主要化合物、交集基因与通路分析结果，绘制成分-靶点-通路网络图。结果 筛选得到左金丸化合物41种、交集基因111个，剔除不含交集基因（靶点）的化学成分后得到化合物31种，槲皮素、黄连素、吴茱萸碱等为左金丸的主要活性成分，AKT1、TP53、HSP90AA1等为主要作用靶点。GO富集分析共获得条目136条，涉及细胞因子受体结合、核受体结合、调控序列特异性DNA结合等多个生物过程，KEGG富集分析得到165条通路。结论 左金丸通过多靶点调控PI3K-Akt信号通路、乙型肝炎通路、IL-17信号通路等治疗原发性肝癌。经生物信息学的基因芯片验证，结果基本相符。
- Abstract:
- Objective To study the mechanism of Zuojin Pills in the treatment of hepatocellular carcinoma based on network pharmacology. Methods The compounds and targets of Zuojin Pills were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The compound s were screened by oral bioavailability (OB) ≥30% and drug-like (DL) ≥0.18 as thresholds, and the targets were input into Uniprot to obtain the gene Symbol . The disease target genes of hepatocellular carcinoma were obtained from GeneCards: The Human Gene Database, and intersection genes of target genes of Zuojin Pills were screened . Cytoscape3.7.1 software was used to draw network diagrams of active ingredient-target and disease-TCM-compound-intersection target (gene) . The protein-protein interaction relationship network was constructed by String. GO enrichment and KEGG pathway enrichment were analyzed by g:Profiler data analysis platform. Combined with the analysis results of major compounds, intersection genes and pathways, the component-target-pathway network diagram was drawn. Results Totally 41 compounds and 111 intersection genes of Zuojin Pills were obtained and chemical components without intersection genes (targets) were removed, and 31 compounds were finally screened. Quercetin, berberine, evodia rutaecarpa alkali were the main active ingredients of Zuojin Pills, and AKT1, TP53, HSP90AA1 were the main targets. After GO enrichment analysis, a total of 136 items meeting the screening criteria were obtained, involving multiple biological processes such as cytokines involved in receptor, nuclear receptors, regulatory sequence specific DNA binding, and 165 were obtained by KEGG enrichment analysis. Conclusion Zuojin Pills can control PI3K-Akt signal pathway, hepatitis B, and IL-17 signal pathway to treat hepatocellular carcinoma. The results are basically consistent through bioinformatics gene chip verification.
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备注/Memo
基金项目：国家自然科学基金（81873303）；湖南省自然科学基金（2016JJ6113）；湖南省卫生健康委科研计划项目（20200949）；湖南中医药大学中医学一流学科开放基金（2018ZYX51）
更新日期/Last Update:
2021-01-25