基于网络药理学探讨黄精防治痛风的机制

Mechanism of Polygonati Rhizoma in Treatment of Gout Based on Network Pharmacology

关键词:  黄精  网络药理学  薯蓣皂苷元  分子对接  痛风

Key words:  Polygonati Rhizoma  network pharmacology  diosgenin  molecular docking  gout

摘要:

目的 运用网络药理学和分子对接技术预测黄精防治痛风的有效成分作用靶点及通路。方法 利用TCMSP和Drugbank数据库获取黄精活性成分及作用靶点，利用TTD、OMIM和GeneCards数据库获得痛风相关靶点，将两者输入Venny 2.1中筛选得到黄精治疗痛风的核心靶点。通过Cytoscape 3.8.0软件构建“中药-成分-靶点-疾病”网络模型，STRING数据库构建PPI网络，Metascape数据库进行GO与KEGG通路富集分析，并用Autodock_vina软件进行分子对接研究。最后，通过LPS结合MSU诱导RAW264.7细胞模拟体外痛风模型，并对预测结果进行验证。结果 预测共得到13种活性成分、90个潜在靶点、1139个痛风相关疾病靶点，19个黄精-痛风交集靶点，涉及MAPK14、CAT、PPARG、NOS2、VEGFA等，并推断其作用机制可能与PI3K-Akt信号通路、血小板激活信号通路、钙信号通路和雌激素信号通路等有关。分子对接结果表明，活性成分与核心靶点的结合能在-10.4~-4.6 kcal·mol^-1，具有较好的结合能力。细胞实验显示，薯蓣皂苷元能够降低p38 MAPK及其上游ERK1/2磷酸化蛋白的表达。结论 黄精防治痛风的生物学机制可能与其调控核心靶点MAPK14有关。

Abstract:

OBJECTIVE To predict the targets and pathways for the main active components of Polygonati Rhizoma in the treatment of gout based on network pharmacology and molecular docking. METHODS The active components and targets of Polygonati Rhizoma were obtained by TCMSP database and Drugbank database. Gout-related target genes were obtained using the TTD database, OMIM database and GeneCards database. Gout-related disease genes and targets of Polygonati Rhizoma were imported into Venny 2.1 to select the targets of Polygonati Rhizoma for gouty treatment. The network map of “TCM-component-target-disease” was constructed using Cytoscape 3.8.0 software. Polygonati Rhizoma-gout common targets were input into the STRING database to build the PPI network. GO and KEGG pathway enrichment analysis was performed using Metascape database, and molecular docking was performed with Autodock_vina software. Finally, The prediction results were verified by preparing an in vitro gout model of RAW264.7 cells induced by LPS combined with MSU. RESULTS Thirteen active components, 90 potential targets, 1 139 gout-related disease targets and 19 effective targets(including MAPK14, CAT, PPARG, NOS2, VEGFA, etc.) for gout control of Polygonati Rhizoma were predicted. The mechanism might be related to PI3K-Akt signaling pathway, platelet activation, calcium signaling pathway and estrogen signaling pathway. Molecular docking results showed that the binding energy of the active component to the core target was -10.4 ~ -4.6 kcal·mol^-1, which had a good binding ability. Cell experiments further showed that diosgenin was able to reduce the expressions of p38 MAPK and its upstream ERK1/2 phosphorylated protein. CONCLUSION The prevention and treatment mechanism of Polygonati Rhizoma against gout might be related to the core target MAPK14.