黄芪汤化学成分分析及其治疗非酒精性脂肪肝病的机制

Chemical constituents of Huangqi decoction and their mechanisms in the treatment of non-alcoholic fatty liver disease

利用高效液相色谱-二极管阵列检测器-蒸发光散射检测器(HPLC-DAD-ELSD)联用技术分析黄芪汤的化学成分,运用网络药理学研究黄芪汤治疗非酒精性脂肪肝病(non-alcoholic fatty liver disease, NAFLD)的多成分、多靶点、多途径作用机制。建立15批黄芪汤水煎液的指纹图谱,使用网络药理学筛选黄芪汤主要活性成分的作用靶点和通路,构建"成分-靶点-通路"网络,预测黄芪汤水煎液治疗NAFLD的作用机制。构建了由27个共有峰组成的黄芪汤水煎液高效液相指纹图谱,采用HPLC-DAD-ELSD技术分析黄芪汤主要化学成分。基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析发现,黄芪汤可能主要通过甘草次酸、异甘草素、甘草酸、黄芪甲苷、甘草素和黄芪皂苷Ⅰ作用于丝氨酸/苏氨酸蛋白激酶1 (RACalpha serine/threonine-protein kinase, AKT1)、白介素-6 (interleukin-6, IL-6)、血管内皮生长因子A (vascular endothelial cell growth factor A, VEGFA)、丝裂原活化蛋白激酶8 (mitogen-activated protein kinase 8, MAPK8)和信号转导与转录激活因子3 (signal transducer and activator of transcription 3, STAT3)潜在靶点,主要通过调节磷脂酰肌醇3激酶/蛋白激酶B、胰岛素抵抗、低氧诱导因子-1和肿瘤坏死因子等信号通路发挥作用。黄芪汤可能通过改善胰岛素抵抗、介导炎症反应、抗氧化应激损伤等机制治疗NAFLD。

We analyzed the main chemical constituents of Huangqi decoction by HPLC coupled with diode array and evaporative light scattering detectors(HPLC-DAD-ELSD). The study on the mechanism of Huangqi decoction was based on network pharmacology and included multi-components, multi-targets, and multi-pathways in the treatment of non-alcoholic fatty liver disease(NAFLD). The chemical "fingerprints" of 15 batches of Huangqi decoction were established. Network pharmacology was used to screen and analyze the targets and pathways of the components of Huangqi decoction, and a "component-target-pathway" network was constructed to predict the mechanism of Huangqi decoction for the treatment of NAFLD. HPLC analysis of Huangqi decoction revealed27 common peaks and the main chemical constituents were identified. Gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis revealed that glycyrrhetinic acid, isoliquiritigenin,glycyrrhizic acid, astragaloside Ⅳ, liquiritigenin, and astragaloside Ⅰ, the main active components of Huangqi decoction, may act on RAC-alpha serine/threonine-protein kinase(AKT1), interleukin-6(IL-6), vascular endothelial cell growth factor A(VEGFA), mitogen-activated protein kinase 8(MAPK8), and signal transducer and activator of transcription 3(STAT3), and may regulate pathways involving phosphatidylinositol-3-kinases(PI3 K)/protein kinase B(AKT), insulin resistance, hypoxia inducible factor-1(HIF-1), tumor necrosis factor(TNF), among others.A decrease in insulin resistance, a reduction of inflammation, and anti-oxidative stress-related effects may be the mechanism of Huangqi decoction for the treatment of NAFLD.