基于网络药理学和分子对接技术探讨桑参饮治疗肺心病的作用机制

Mechanism of Sangshen Yin(桑参饮)in treating pulmonary heart disease based on network pharmacology and molecular docking

目的基于网络药理学和分子对接技术探讨桑参饮治疗肺心病的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、中医药综合数据库(TCMID)及中药分子机制生物信息学分析工具(BATMAN-TCM)获取桑参饮的有效成分和作用靶点,从疗效药靶数据库(TTD)等筛选肺心病的疾病靶点,将二者交集靶点进行京都基因与基因组百科全书(KEGG)富集分析;采用Cytoscape 3.7.0软件构建“中药-有效成分-靶点-通路”网络,并利用网络拓扑分析筛选核心靶点及核心通路;采用分子对接技术对核心靶点及其相互作用的有效成分进行验证。结果共获得有效成分68种,对应靶点81个,核心靶点主要包括环加氧酶2(PTGS2)、丝氨酸/苏氨酸蛋白激酶(AKT1)、雌激素受体β(ESR2)、诱导型一氧化氮合酶(NOS2)、基质金属蛋白酶9(MMP9)、过氧化物酶体增殖物激活受体γ(PPARG)、肿瘤坏死因子(TNF)等;通过KEGG富集分析得到通路25条,免疫球蛋白E受体信号通路、肿瘤坏死因子信号通路等通路是桑参饮治疗肺心病的核心信号通路。分子对接结果显示,核心靶点与核心成分具有较强的亲和力。结论桑参饮中的常春藤皂苷元、黄芩素等成分与PTGS2、AKT1、ESR2等靶点作用,通过调节炎症反应、氧化应激、能量代谢和血管生成等治疗肺心病。

Objective To investigate the mechanism of Sangshen Yin(桑参饮)in treating chronic pulmonary heart disease using network pharmacology and molecular docking technology.Methods The chemical constituents and targets of Sangshen Yin were obtained from TCMSP and BATMAN-TCM,while the disease targets of pulmonary heart disease were screened from TTD and other therapeutic drug targets.The intersection targets of the two sets were enriched using the Kyoto Encyclopedia of Genes and Genomes(KEGG).A"TCM-chemical constituents-target-pathway"network was constructed using Cytoscape 3.7.0 software,with core targets and pathways identified through network topology analysis.Molecular docking technology was employed to verify the interaction between the chemical composition of the core target.Results A total of 68 chemical constituents corresponding to 81 targets were obtained.The core targets mainly include cyclooxygenase-2(PTGS2),serine/threonine protein kinase(AKT1),estrogen receptorβ(ESR2),inducible nitric oxide synthase(NOS2),matrix metalloproteinase 9(MMP9),peroxisome proliferator-activated receptorγ(PPARG),tumor necrosis factor(TNF),etc.KEGG enrichment analysis revealed 25 pathways,with immunoglobulin E receptor signaling pathway and tumor necrosis factor signaling pathway identified as core signaling pathways for treating pulmonary heart disease with Sangshen Yin.Results from molecular docking demonstrated a strong affinity between the core target and its components.Conclusion Hederagenin,baicalein,and other components of Sangshen Yin can act on PTGS2,AKT1,ESR2,among other targets,thereby treating pulmonary heart disease by regulating inflammation,oxidative stress,energy metabolism,angiogenesis,etc.