基于健脾法和网络药理学探讨“茯苓-白术”药对治疗非酒精性脂肪性肝病的作用机制

Mechanism of Fuling-Baizhu in the treatment of non-alcoholic fatty liver disease from the perspective of network pharmacology based on"strengthening spleen"

目的:基于健脾法,借助网络药理学探讨“茯苓-白术”药对(FB)治疗非酒精性脂肪性肝病(NAFLD)的作用机制。方法:通过TCMSP与Swiss Target Prediction数据库获取茯苓与白术的活性成分及作用靶点,利用GeneCards和DisGeNET数据库检索NAFLD相关靶点,将上述交集靶点输入STRING数据库,从而获取蛋白质互作关系网络。运用DAVID6.7数据库进行GO与KEGG富集分析,Cytoscape 3.7.2软件构建“药对成分-异常靶点-通路”网络图,AutoVina软件进行分子对接。结果:共得到20个活性成分,206个潜在靶点、2088个疾病靶点,88个交集靶点。GO富集主要涉及类固醇激素介导的信号通路、RNA聚合酶Ⅱ对转录的正调控、细胞对缺氧的反应等,KEGG主要与胰岛素信号通路、PPAR信号通道和胰岛素抵抗等相关。网络分析结果表明,FB治疗NAFLD的核心成分为齿孔酸、多孔菌酸C、茯苓酸C、去氢齿孔酸,核心靶点为TNF、MAPK3、PIK3CA、NR1H3。分子对接结果显示核心靶点与核心成分的结合能均小于≤-5.0 kcal/mol,展现出较好的亲和力。结论:茯苓-白术药对主要通过促进肝脏脂肪代谢及抑制部分炎症因子而发挥抗炎护肝作用,从而起到治疗NAFLD的作用。

Objective:To explore the mechanism of Fuling-Baizhu(FB)in the treatment of non-alcoholic fatty liver disease(NAFLD)from the perspective of network pharmacology based on the theory of"strengthening spleen".Methods:Traditional Chinese medicine systems pharmacology database(TCMSP)and SwissTargetPrediction database were used to search the chemically active components and their respective targets of Fuling and Baizhu,and GeneCards database and DisGeNET database were used to collect the NAFLD-related targets.The intersection targets of the FB and NAFLD were input into the online database of STRING protein interaction,thus the protein-protein interaction(PPI)network was obtained.Then GO and KEGG enrichment analysis was carried out by DAVID6.7 database and the"FB active components-abnormal targets-pathways"network diagram was constructed by Cytoscape 3.7.2 software.Finally,autoVina software was used for molecular docking.Results:A total of 20 active components,206 potential targets,2088 targets of NAFLD,and 88 targets of FB-NAFLD was obtained.GO enrichment mainly involved steroid hormone mediated signaling pathway,positive regulation of transcription from RNA polymeraseⅡpromoter,and cellular response to hypoxia.KEGG enrichment mainly involved steroid hormone mediated signaling pathway,PPAR signaling pathway,and Insulin resistance.The network analysis results showed that the key chemical components of FB in the treatment of NAFLD mainly involve eburicoic acid,polyporenic acid C and poricoic acid C,and the key targets included TNF,MAPK3,PIK3CA,and NR1H3.And the results of molecular docking showed that the binding energies of between them were all less than-5.0 kJ/mol,showing a good affinity.Conclusion:FB has an anti-inflammatory and liver-protective effect mainly by promoting liver fat metabolism and inhibiting some inflammatory factors,thereby having the effect of treating NAFLD.