基于网络药理学原理的黄芪-金银花药对干预急性呼吸窘迫综合征的分子机制研究

Molecular mechanism research of Stragalus Radix and Lonicerae Japonicae Flos drug pair for acute respiratory distress syndrome based on the principle of network pharmacology

关键词:  黄芪-金银花  急性呼吸窘迫综合征  益气化瘀解毒方  网络药理学  机制

Key words:  Stragalus Radix and Lonicerae Japonicae Flos  acute respiratory distress syndrome  Yiqi Huayu Jiedu Decoction  network pharmacology  mechanism

摘要:

[目的]基于网络药理学原理，探讨课题组前期实验有效方益气化瘀解毒方核心药对黄芪-金银花干预急性呼吸窘迫综合征（ARDS）的分子通路及作用机制。[方法]应用整合药理学平台对黄芪、金银花化学成分及ARDS疾病候选靶标进行收集，根据结构相似性原理选取相似性分数≥0.8的所有药物靶标作为“黄芪-金银花”药对的潜在作用靶标，建立药物候选靶标信息数据库，通过该平台的蛋白质-蛋白质相互作用信息（PPI）数据库，获得“黄芪-金银花”药对作用的潜在靶标与ARDS疾病靶标之间的蛋白质-蛋白质相互作用信息（PPI），通过网络分析，构建“中药-核心成分-关键靶标-主要通路”的可视化网络图，进一步明确中药干预疾病的作用机制。[结果]黄芪-金银花药对共预测得到76个活性成分，其中黄芪化合物成分29个，金银花化合物成分47个。其干预ARDS作用涉及的前100个核心靶标中已知治疗ARDS的直接靶标（known disease target）78个，潜在药物靶标（putative drug target）3个，共同靶标（common target）2个；其干预ARDS的作用涉及ErbB信号通路、FoxO信号转导通路、Ras信号途径、丝裂原活化蛋白激酶（MAPK）信号通路、磷脂酰肌醇3-激酶（PI3K）-蛋白激酶B（AKT）信号通路、神经营养因子信号转导通路、细胞生长与死亡等相关生物过程和代谢通路。[结论]黄芪-金银花药对主要活性成分可针对多个靶点、多条通路发挥干预ARDS的作用，其作用与TSC1、NSDHL、GRB2、MYC、MAP2K等关键靶标及ErbB信号通路、FoxO信号转导通路、Ras信号途径、MAPK信号通路和PI3K-AKT信号通路等有关。

Abstract:

[Objective] Based on the principle of network pharmacology, to clarified the molecular pathway and mechanism of Stragalus Radix and Lonicerae Japonicae Flos core drug pair of Yiqi Huayu Jiedu Decoction on acute respiratory distress syndrome (ARDS).[Methods] The chemical constituents of Stragalus Radix and Lonicerae Japonicae Flos and the candidate targets of ARDS were collected by the integrated pharmacological platform. According to the principle of structural similarity, all the drug targets with similarity score (≥ 0.8) were selected as the potential targets of the "Stragalus Radix and Lonicerae Japonicae Flos" pair, and the candidate target information database was established. PPI (Protein Protein Interaction Information) database was used to obtain the PPI between the potential target of "Stragalus Radix and Lonicerae Japonicae Flos" and the disease target of ARDS. Through network analysis, a visualized network diagram of "traditional Chinese medicine-core component-key target-main pathway" was constructed to further illustrate. The mechanism of Chinese medicine intervening disease is determined.[Results] A total of 76 active constituents were predicted by the Stragalus Radix and Lonicerae Japonicae Flos pair, 29 of which were Astragalus membranaceus and 47 of which were Lonicerae Japonicae Flos. Among the first 100 core targets, 78 known disease targets, 3 putative drug targets and 2 common Targets were involved in the intervention of ARDS, including ErbB signaling pathway, FoxO signaling pathway and Ras signal pathway, MAPK signal pathway, PI3K-AKT signal pathway, neurotrophic factor signal transduction pathway, cell growth and death and other related biological processes and metabolic pathways.[Conclusion] Main active ingredient of Stragalus Radix and Lonicerae Japonicae Flos drug pair can interfere with ARDS by targeting multiple targets and multiple pathways. Its effect is related to TSC1, NSDHL, GRB2, MYC, MAP2K, ErbB signaling pathway, FoxO signaling pathway, Ras signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway and so on.