| 基于网络药理学和分子对接探讨四物汤防治辐射损伤的作用机制 |
| Mechanism of Siwu Decoction on radiation syndrome based on network pharmacology and molecular dockingTeng Hao chen1,Yang Yuwei1,Xu Wenqing1,Zhou Xiaoliang1 |
| DOI： |
| 中文关键词: 网络药理学 分子对接 四物汤 辐射损伤 HIF-1信号通路 |
| 英文关键词: Network pharmacology Molecular docking Siwu Decoction radiation syndrome HIF-1 signaling pathway |
| 基金项目:国家自然科学基金资助项目（No.82203970） 天津市科技计划项目（23JCZDJC00300) |
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| 中文摘要: |
| 【】目的 基于网络药理学和分子对接技术探究四物汤防治辐射损伤的作用机制。方法 通过中药系统药理学数据库分析平台(TCMSP)与文献报道获取熟地黄、白芍、川芎、当归的主要活性成分及其靶点,根据生物利用度(bioavailability,OB)与类药性(drug-like properties, DL)进一步筛选已获取的中药活性组分；通过在线人类孟德尔遗传(OMIM)、遗传药理学和药物基因组学(PharmGkb)、Genecards和Drugbank数据库获取辐射损伤(radiation syndrome, RS)的主要作用靶点；通过Venn Diagram得到四物汤与辐射损伤RS交集靶点,构建“成分-靶点”网络；利用String和Cytoscape对四物汤作用于RS的相关靶点进行蛋白质-蛋白质相互作用(protein-protein interaction network,PPI)分析,构建PPI网络；最后,采用David和Metascape平台分析四物汤靶点参与RS的生物过程及通路,构建“活性成分-疾病-通路”网络,并运用AutoDock及Pymol对靶点与相应活性成分进行分子对接验证。结果 从四物汤中筛选得到34种活性成分及855个作用靶点,与11405个辐射损伤RS相关靶点取交集,得到719个共同靶点；四物汤含有去甲齐墩果酸、杨梅酮、芍药苷、儿茶素等特征活性成分,防治辐射损伤的核心靶点包括磷脂酰肌醇-3-激酶(phosphatidylino-sitol 3-kinases,PI3Ks)、乏氧诱导因子1(hypoxia inducible factor 1,HIF-1)、肿瘤蛋白p53(tumor protein P53,TP53)、信号转导及转录激活因子3(signal transducer and activator of transcription 3,STAT3)、丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)等,这些核心靶点特异表达富集于骨髓、血液、脾脏等；并通过调控乏氧应答、凋亡、PI3K/Akt及MAPK级联反应等信号通路发挥功效。分子对接结果显示,筛选的主要活性成分与HIF1A靶点具有较好的结合活性,推测四物汤有效成分亦可通过抑制铁死亡防治辐射损伤,但还需进一步验证。结论 四物汤通过多成分、多靶点、多通路发挥防治辐射损伤作用,且与HIF-1信 |
| 英文摘要: |
| 【】Objective This study was aimed to reveal the mechanism of Siwu Decoction (四物汤) on radiation syndrome based on network pharmacology and molecular docking. Methods Main chemical components and targets of Rehmanniae Radix Praeparata, Paeoniae Radix Alba, Chuanxiong Rhizoma and Angelicae Sinensis Radix were obtained from TCMSP database and reports, and active components of these were further screened according to bioavailability (OB) and drug-like properties (DL). Main targets of radiation syndrome (RS) were obtained from databases of Online Mendelian Inheritance in Man (OMIM), PharmacogenomicsKnowledgebase (PharmGkb), Genecards, and Drugbank. Common targets of Siwu Decoction and radiation syndrome were obtained by Venn Diagram. String and Cytoscape were further used to analyze protein-protein interaction (PPI) of those common targets and construct PPI network. Biological processes and pathways of Siwu Decoction against RS were analyzed by Metascape and David platform, and then a network of “active component-di |
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