Qiang-Gan formula extract improves non-alcoholic steatohepatitis via regulating bile acid metabolism and gut microbiota in mice
Qiang-Gan formula extract improves non-alcoholic steatohepatitis via regulating bile acid metabolism and gut microbiota in mice
复制标题
强肝配方提取物通过调节小鼠胆汁酸代谢和肠道微生物群改善非酒精性脂肪性肝炎
DOI：
10.1016/j.jep.2020.112896
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发表时间：
2020-08-10
影响因子：
5.4
通讯作者：
Ji, Guang
中科院分区：
文献类型：
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作者：
Li, Qiong;Li, Meng;Ji, Guang
民族药理学相关性：强肝方是我国治疗肝病的常用中药，本研究旨在探讨强肝方提取物（QGE）对非酒精性脂肪性肝炎（NASH）的治疗作用及其可能的作用机制。通过管饲法向蛋氨酸和胆碱缺乏饮食诱导的NASH小鼠施用QGE四周。观察肝组织病理学改变及血清谷丙转氨酶（ALT）、谷草转氨酶（AST）水平。采用气相色谱-质谱联用技术分析血清、肝脏和粪便样品中胆汁酸的组成，并采用16 S rDNA测序技术检测粪便微生物。肝G蛋白偶联胆汁酸受体1（TGR 5）、法尼基肽X受体（FXR）、肿瘤坏死因子-α的表达（TNF-α）、白细胞介素1 β（IL-1 β）以及核因子κ B中的分子分别通过免疫组织化学染色、RT-qPCR或Western印迹法检测（NF-κ B）途径。结果：QGE减轻NASH小鼠肝脏炎症，降低血清ALT和AST水平以及肝脏TNF-α和IL-1 β表达。在该动物模型中，它还降低了肝脏和血清BA浓度，并增加了粪便石胆酸（LCA）的产生。QGE改变了肠道微生物群的结构，主要是增加NASH小鼠中产生LCA的细菌拟杆菌和梭菌。结论：QGE对NASH小鼠具有保护作用，其机制可能与调节肠道菌群介导的LCA产生、促进TGR 5表达、抑制NF-κ B活化有关。
Ethnopharmacological relevance: Qiang-Gan formula is a traditional Chinese medicine formula, which has been widely used in treating liver diseases in China.Aim of the study: To investigate the effect of Qiang-Gan formula extract (QGE) on non-alcoholic steatohepatitis (NASH) and its underlying possible mechanisms.Materials and methods: The high-performance liquid chromatography finger-print method was used for the quality control of chemical components in QGE. Methionine- and choline-deficient diet-induced NASH mice were administrated with QGE via gavage for four weeks. Phenotypic parameters including liver histological change as well as serum levels of alanine transaminase (ALT), aspartate transaminase (AST) were detected. Bile acid profile in the serum, liver and fecal samples was analyzed by gas chromatography-mass spectrometer technique, and fecal microbiota was detected by 16S rDNA sequencing. Expression of liver G protein-coupled bile acid receptor 1 (TGR5), farnesiod X receptor (FXR), tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) as well as molecules in nuclear factor kappa B (NF-kappa B) pathway was assayed by immunohistochemistry staining, RT-qPCR, or Western blot, respectively.Results: QGE alleviated liver inflammation, reduced serum ALT and AST levels and liver TNF-alpha and IL-1 beta expression in NASH mice. It also decreased liver and serum BA concentration and increased fecal lithocholic-acid (LCA) production in this animal model. QGE altered the structure of gut microbiota, predominantly increased LCA-producing bacteria Bacteroides and Clostridium in NASH mice. In addition, the expression of liver TGR5 but not FXR was increased, and the molecules in NF-kappa B pathway were decreased in QGE-treated NASH mice.Conclusions: QGE was effective in preventing NASH, possibly by regulation of gut microbiota-mediated LCA production, promotion of TGR5 expression and suppression of the NF-kappa B activation.