首页|基于营卫理论探讨桂枝-赤芍配伍重塑肿瘤血管微环境的网络药理学机制

基于营卫理论探讨桂枝-赤芍配伍重塑肿瘤血管微环境的网络药理学机制

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目的:采用网络药理学方法预测桂枝-赤芍配伍影响肿瘤血管生成的潜在靶点和通路，从分子网络药理学水平探索该配伍重塑肿瘤血管微环境的网络药理学机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)检索桂枝、赤芍的化学成分和潜在靶点，选择口服生物利用度≥30%和类药性≥0。18 作为化学成分筛选条件;在GeneCards数据库中检索血管生成的靶点;利用Cytoscape 3。6。0 软件绘制桂枝-赤芍配伍-化合物-靶点-血管生成网络;使用STRING 11。0 在线软件构建蛋白质-蛋白质相互作用(PPI)网络并挖掘核心靶点;采用David Bioinformatics Resources数据库对该复方活性成分潜在的靶点网络中的蛋白进行基因本体(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:桂枝-赤芍配伍的 33 种有效成分作用于血管生成过程的 77 个靶点，PPI网络的核心靶点包括蛋白激酶B(Akt)1、JUN、白细胞介素 6、基质金属蛋白酶、血管内皮生长因子A、一氧化氮合酶 2 和缺氧诱导因子-1α等多个蛋白。GO功能富集分析提示，该配伍的关键蛋白主要参与了DNA结合转录激活剂活性、血红素结合、抗氧化活性、核受体活性和转录因子活性等生物过程。KEGG通路富集分析显示，该配伍参与了缺氧诱导因子-1(HIF-1)信号通路、肿瘤蛋白 53 信号通路、细胞凋亡信号通路、表皮生长因子受体酪氨酸激酶抑制剂耐药信号通路、血管内皮生长因子(VEGF)信号通路和磷脂酰肌醇 3 激酶-Akt信号通路等，提示桂枝-赤芍配伍与肿瘤血管生成的关系最为密切。结论:桂枝-赤芍配伍中的黄芩素、谷甾醇和鞣花酸等成分可能通过HIF-1 信号通路、VEGF信号通路影响肿瘤血管生成，干预肿瘤的生物学行为。
Network Pharmacological Mechanism of Cinnamomi Ramulus-Radix Paeoniae Rubra Compatibility in Remodeling Tumor Vascular Microenvironment Based on Theory of Nutritive Qi and Defensive Qi
OBJECTIVE:To probe into the predict the potential targets and pathways of Cinnamomi Ramulus-Radix Paeoniae Rubra compatibility affecting tumor angiogenesis by using network pharmacology,and to explore the network pharmacological mechanism of the compatible structure to remodel the tumor vascular microenvironment from the molecular network pharmacological level.METHODS:Chemical components and potential targets of Cinnamomi Ramulus and Radix Paeoniae Rubra were retrieved based on the traditional Chinese medicines systems pharmacology platform(TCMSP).Oral bioavailability≥30%and drug-like properties≥0.18 were selected as chemical composition screening conditions.The target of angiogenesis was searched in GeneCards database.Cytoscape 3.6.0 software was used to draw the network diagram of Cinnamomi Ramulus-Radix Paeoniae Rubra-compound-targets-angiogenesis.STRING 11.0 online software was used to construct the protein-protein Interaction(PPI)network and mine the core targets.Gene ontology(GO)function enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed for proteins in the potential target network of the compound active component by using David Bioinformatics Resources database.RESULTS:Totally 33 active components of Cinnamomi Ramulus-Radix Paeoniae Rubra were used in 77 targets of angiogenesis.Core targets of PPI network included protein kinase B(Akt)1,JUN,interleukin 6,matrix metalloproteinases,vascular endothelial growth factor A,nitric oxide synthase 2,and hypoxia-inducible factor-1α.GO functional enrichment analysis suggested that the key proteins of compatibility were mainly biological processes such as DNA-binding transcriptional activator activity,heme-binding activity,antioxidant activity,nuclear receptor activity and transcription factor activity.KEGG pathway enrichment analysis showed that the compatibility was involved in hypoxia-inducible factor-1(HIF-1)signaling pathway,p53 signaling pathway,apoptosis signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitor resistance signaling pathway,vascular endothelial growth factor(VEGF)signaling pathway,and phosphatidylinositol 3-kinase-Akt signaling pathway,suggesting that Cinnamomi Ramulus-Radix Paeoniae Rubra compatibility was most closely related to tumor angiogenesis.CONCLUSIONS:Components such as baicalein,sitosterol and ellagic acid in Cinnamomi Ramulus-Radix Paeoniae Rubra compatibility may affect tumor angiogenesis and intervene in the biological behavior of tumors through the HIF-1 signaling pathway and VEGF signaling pathway.

Theory of nutritive Qi and defensive QiCinnamomi RamulusRadix Paeoniae RubraCompatibilityTumor vascular microenvironmentNetwork pharmacology

黄菁、汪宗清、李思泽、陈婷、沈红梅

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昆明医科大学第三附属医院/云南省肿瘤医院中西医结合科,昆明 650118

南京中医药大学第一临床医学院,南京 210000

安宁市第一人民医院康复医学科,云南 安宁 650300

云南中医药大学第一临床医学院,昆明 650032

昆明医科大学第三附属医院/云南省肿瘤医院核医学科,昆明 650118

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营卫 桂枝 赤芍 配伍 肿瘤血管微环境 网络药理学

国家自然科学基金地区科学基金云南省教育厅科研项目云南省科技厅-昆明医科大学应用基础研究联合专项面上项目全国中医药创新骨干人才培训项目云南省高层次卫生健康技术人才培养项目(2019)全国老中医药专家学术经验继承项目(第七批)

819604262019J1290202001AY070001-245国中医药人教函[2019]128号H-2019077国中医药人教函[2022]76号

2024

10.14009/j.issn.1672-2124.2024.03.003

中国医院用药评价与分析
中国医药生物技术协会，中国药房杂志社

中国医院用药评价与分析

CSTPCD
影响因子：1.142
ISSN：1672-2124
年,卷(期)：2024.24(3)
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