基于系统药理学的柴胡防治非酒精性脂肪肝作用机制研究

Study of the mechanism of Bupleuri Radix in the preventing and treatment of non-alcoholic fatty liver based on systemic pharmacology

【目的】探究柴胡对非酒精性脂肪性肝病(NAFLD)的防治作用及机制。【方法】借助TCMSP数据库及查阅文献获取柴胡化学成分及其作用靶点,并利用Gene Cards、OMIM等数据库获取NAFLD疾病靶点。筛选二者间共有靶点进行蛋白质互作、KEGG、GO富集与分子对接分析,以挖掘柴胡防治NAFLD潜在活性成分及作用机制。最后,通过高脂饲料复合高糖饮水建立NAFLD小鼠模型,验证柴胡治疗效果及作用机制。【结果】柴胡可通过18个潜在活性成分直接作用于99个靶点来防治NAFLD,其中槲皮素、山奈酚、异鼠李素为其核心活性成分,AKT1、TNF、ESR1为其核心作用靶点。富集分析表明,柴胡可能通过干预PI3K-AKT、MAPK及TNF等信号通路来防治NAFLD。动物试验结果表明,柴胡治疗能显著降低NAFLD小鼠血清AST、ALT水平,改善NAFLD小鼠肝脏脂肪变性,并回调PI3K-AKT通路中AKT和MAPK通路中SREBP-1在肝脏组织中的表达。【结论】柴胡可有效的防治NAFLD,其作用机制与调控PI3K-AKT和MAPK信号通路密切相关。

【Objective】To investigate the prevention and treatment effect and mechanism of Bupleurum Bupleuri Radix on non-alcoholic fatty liver disease(NAFLD).【Method】Chemical constituents and targets of Bupleuri Radix were obtained from TCMSP database and literature review,and disease targets of NAFLD were obtained from Gene Cards and OMIM databases.Protein interaction analysis,KEGG and GO enrichment analysis and molecular docking were performed to screen common targets between Bupleuri Radix and NAFLD,so as to explore potential active components and mechanism of action of Bupleuri Radix against NAFLD.Finally,high fat diet combined with high sugar drinking water was used to establish NAFLD mouse model to verify the therapeutic effect and mechanism of Bupleuri Radix.【Result】Bupleuri Radix could prevent and treat NAFLD by directly regulating 99 targets through 18 potential active components,of which quercetin,kaempferol and isorhamnetin were the core active components,and AKT1,TNF and ESR1 were the core targets.Enrichment analysis showed that Bupleuri Radix could prevent and treat NAFLD mainly by interfering with PI3K-AKT,MAPK and TNF signaling pathways.The results of animal experiments showed that Bupleuri Radix could reduce the serum AST and ALT levels in NAFLD mice and improve the liver steatosis in NAFLD mice.【Conclusion】Bupleuri Radix can effectively prevent and control NAFLD,and its mechanism is closely related to the regulation of PI3K-AKT and MAPK signaling pathways.