| 引用本文:贺忠宁1，陈鸿2，郭秋均1，花宝金1，李丛煌1.基于网络药理学及实验验证分析西黄丸治疗胃癌血瘀证的潜在活性成分及作用机制[J].世界中医药,2023,(02):. |
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| 基于网络药理学及实验验证分析西黄丸治疗胃癌血瘀证的潜在活性成分及作用机制 |
| Active Components and Mechanism of Xihuang Pills against Gastric Cancer with Blood Stasis Syndrome：Based on Network Pharmacology and Experimental Verification |
| 投稿时间：2022-06-11 |
| DOI：10.3969/j.issn.1673-7202.2023.02.003 |
| 中文关键词: 中医药整合药理学 TCMIP V2.0 西黄丸 胃癌 血瘀证 调气解毒 分子对接 病-证-方 |
| English Keywords:Integrative Pharmacology of traditional Chinese medicine TCMIP V2.0 Xihuang Pills Gastric cancer Blood stasis Regulating qi and detoxifying Molecular docking Disease-syndrome-prescription |
| 基金项目:北京市自然科学基金项目(7212189) |
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| 中文摘要: |
| 目的:应用中医药整合药理学研究平台(TCMIP V2.0)预测西黄丸治疗胃癌血瘀证的潜在活性成分,并初步探讨其分子机制。方法:利用TCMIP V2.0平台中药材数据库及中药分子机制模型数据库(BATMAN-TCM)，收集西黄丸已报道的化学成分信息;利用中药(含方剂)靶标预测功能,收集西黄丸的候选靶标谱;利用疾病数据库,收集胃癌疾病及血瘀证证候基因集;利用病证方关联分析模块,构建“病-证-方”关联网络,由网络拓扑特征值确定核心网络;利用David 6.8平台对“病-证-方”的核心网络进行生物学功能分析,包括基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路富集分析;根据化学成分对应的靶点个数和频次,圈定西黄丸治疗胃癌血瘀证的潜在核心成分及其对应的靶点和通路信息;利用Cytoscape 3.8.0软件绘制“核心成分-核心靶点-核心通路”图;再利用Autodock 4.2对主要成分和核心靶点进行分子对接验证。结果:西黄丸主要通过4味中药、13个核心化学成分、19个核心靶标、33条核心通路发挥其治疗胃癌血瘀证的药理作用。其治疗的机制可能主要集中麝香、乳香等两味中药,涉及的通路主要包括肿瘤通路、致癌相关通路、免疫系统通路、内分泌与代谢相关通路等; 磷酸肌醇3激酶(PIK3CG)、磷脂酰肌醇3(PIK3R1)、核因子B1(NFKB1)、肿瘤蛋白P53(TP53)、细胞周期蛋白42(CDC42)等靶点可能在其治疗胃癌血瘀证中发挥了重要的作用。分子对接结果显示核心成分与靶点之间有较强的结合力。体外实验发现:西黄丸可以显著抑制胃癌(MGC-803)细胞拟态管道的形成(P<0.01),且抑制作用等同于低氧诱导因子-1α(Hypoxia Inducible Factor-1,HIF-1α)抑制剂2-甲氧基雌二醇(2-ME)。体内实验发现:西黄丸及2-ME均可以显著降低小鼠胃癌组织中拟态管道的形成数目,二者的作用相似。结论：西黄丸的潜在化学成分可以治疗胃癌血瘀证患者，还能抑制胃癌小鼠血管生成拟态的形成。 |
| English Summary: |
| To predict the potential active components of Xihuang Pills against gastric cancer with blood stasis syndrome based on Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP V2.0) and to explore the molecular mechanism.Methods:The chemical constituents of Xihuang Pills were retrieved from TCMIP V2.0 and a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM), and the candidate targets of Xihuang Pills were predicted.Genes related to the gastric cancer and blood stasis syndrome were screened out and the disease-syndrome-prescription network was constructed.The core network was determined based on the network topology eigenvalue and David 6.8 was employed for the Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the core network.According to the number and frequency of the chemical components, the potential core components of Xihuang Pills against gastric cancer with the blood stasis syndrome and the corresponding targets and pathways were determined.Cytoscape 3.8.0 was used to plot the “core component-core target-core pathway” network, and Autodock 4.2 was applied for the docking of major components and core targets.Results:Xihuang Pills exerts therapeutic effect on gastric cancer with blood stasis syndrome through 4 medicinals, 13 core chemical components, 19 core targets, and 33 core pathways.The main medicinals were Moschus and Olibanum, and the pathways involved mainly included tumor pathway, carcinogenesis-related pathway, immune system pathway, and endocrine and metabolism-related pathway.Phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit gamma (PIK3CG), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), nuclear factor kappa B subunit 1 (NFKB1), tumor protein p53 (TP53), and cell division cycle 42 (CDC42) may play an important role in the treatment of blood stasis syndrome of gastric cancer.Molecular docking showed high binding affinity between the core components and the targets.In vitro experiments showed that Xihuang pills significantly inhibited the formation of mimicry channels in gastric cancer (MGC-803) cells (P<0.01), and the inhibitory effect was equivalent to 2-methoxy-estradiol (2-ME), an inhibitor of Hypoxia Inducible Faction-1 (HIF-1α).In vivo experiments showed that both Xihuang Pills and 2-ME could significantly reduce the number of mimicry channels in mouse gastric cancer tissue, and their effects were similar.Conclusion:The potential chemical components of Xihuang pills can treat the patients with blood stasis syndrome of gastric cancer and inhibit the formation of angiogenic mimicry in mice with gastric cancer. |
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