| 摘要: |
| 目的：采用网络药理学方法和分子对接技术研究西黄丸治疗胰腺神经内分泌瘤（pNET）的作用机制。方法：应用TCMSP、HERB等数据库及相关文献获取西黄丸的活性成分和作用靶点，通过GEO、GeneCards、OMIM等数据库获取pNET的疾病靶点，筛选出与西黄丸的共同靶点，通过R 4.1.2软件对共同靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析，利用STRING 11.5构建共同靶点蛋白质-蛋白质相互作用网络（PPI），应用Cytoscape 3.9.0软件构建西黄丸活性成分-pNET疾病靶点交集网络及筛选核心靶点，通过分子对接对核心靶点与活性成分进行验证。结果：获得西黄丸治疗pNET的活性成分66种，主要有槲皮素、β-谷甾醇、鞣花酸、雌二醇、桑色素等；筛选得到西黄丸作用于pNET的靶点148个，核心靶点有转录因子AP-1（JUN)、肿瘤抑制蛋白53（TP53）、细胞性骨髓细胞瘤病病毒癌（MYC）、雌激素受体1（ESR1）、缺氧诱导因子-1α(HIF1A)、丝裂原活化蛋白激酶1（MAPK1）等。GO功能主要富集在对外来刺激的反应、膜筏、DNA-结合转录因子结合等方面；KEGG通路主要富集在脂质与化学致癌-受体激活、肿瘤蛋白53（p53）等信号通路。分子对接结果显示，JUN与β-谷甾醇和槲皮素，TP53与槲皮素，MYC与槲皮素，ESR1与鞣花酸、雌二醇、桑色素和phellamurin_qt，HIF1A与槲皮素，MAPK1与槲皮素、muscol和胆固醇结合效果良好。结论：西黄丸治疗pNET通过多成分、多靶点、多通路的复杂网络起效，为后续相关实验研究提供了思路和理论依据。 |
| 关键词: 胰腺神经内分泌瘤 西黄丸 作用机制 网络药理学 分子对接 |
| DOI： |
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| Mechanism of action of Xihuang Pill in treatment of pancreatic neuroendocrine tumor：A study based on network pharmacology and molecular docking |
| TIAN Chao,XU Peng,KANG Chao |
| (Shaanxi Provincial Hospital of Traditional Chinese Medicine，Xi’an 710003，Shaanxi，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of Xihuang Pill in the treatment of pancreatic neuroendocrine tumor (pNET) based on network pharmacology and molecular docking.Methods：TCMSP and HERB databases and related articles were searched to obtain the active components and action targets of Xihuang Pill，and GEO，GeneCards，and OMIM databases were used to obtain the disease targets of pNET.The intersecting targets were obtained，and R 4.1.2 software was used to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the intersecting targets.STRING 11.5 was used to construct a protein-protein interaction network for the intersecting targets.Cytoscape 3.9.0 was used to construct a network for the active components of Xihuang Pill and the disease targets of pNET and identify the core targets，and molecular docking was used to validate the interaction between core targets and active components.Results：A total of 66 active components were obtained for Xihuang Pill in the treatment of pNET，including quercetin，beta-sitosterol，ellagic acid，estradiol，and morin.A total of 148 targets were obtained for the action of Xihuang Pill on pNET，and the core targets included JUN，TP53，MYC，ESR1，HIF1A，and MAPK1.GO functions were mainly enriched in response to external stimuli，membrane raft，and DNA-transcription factor binding，and KEGG pathways were mainly enriched in the lipid signaling pathway，the chemical carcinogenesis-receptor activation pathway，and the tumor protein p53 pathway.Molecular docking showed a good binding effect between JUN/beta-sitosterol and quercetin，between TP53 and quercetin，between MYC and quercetin，between ESR1 and ellagic acid/estradiol/morin/phellamurin_qt，between HIF1A and quercetin，and between MAPK1 and quercetin/muscol/cholesterol.Conclusion：Xihuang Pill exerts a therapeutic effect on pNET through a complex network involving multiple components，targets，and pathways，which provides a theoretical basis for subsequent studies. |
| Key words: pancreatic neuroendocrine tumor Xihuang Pill mechanism of action network pharmacology molecular docking |
