The probiotic effects of AB23A on high-fat-diet-induced non-alcoholic fatty liver disease in mice may be associated with suppressing the serum levels of lipopolysaccharides and branched-chain amino acids
The probiotic effects of AB23A on high-fat-diet-induced non-alcoholic fatty liver disease in mice may be associated with suppressing the serum levels of lipopolysaccharides and branched-chain amino acids
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AB23A 对高脂饮食诱导的小鼠非酒精性脂肪肝的益生作用可能与抑制脂多糖和支链氨基酸的血清水平有关
DOI：
10.1016/j.abb.2021.109080
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发表时间：
2021-11-06
影响因子：
3.9
通讯作者：
Zhou, Benjie
中科院分区：
文献类型：
--
作者：
Xia, Fan;Xiang, Shijian;Zhou, Benjie
泽泻醇B 23-乙酸酯（AB 23 A）是从中药泽泻中分离得到的一种天然三萜类化合物，具有广泛的药用价值。以前的研究已经证明了AB 23 A对非酒精性脂肪肝（NAFLD）的有益作用，但肠道微生物群与AB 23 A的抗NAFLD作用之间的功能相互作用尚不清楚。在这项研究中，我们研究了用AB 23 A实验性治疗对肥胖模型NAFLD中肠道微生物群失调的益处。给C57 BL/6 J小鼠施用含有或不含有AB 23 A的高脂肪饮食（HFD）12周。AB 23 A显著改善了HFD喂养小鼠的代谢表型。此外，基于16 S rRNA基因的扩增子测序结果显示，AB 23 A不仅降低了厚壁菌门/拟杆菌门比值和放线菌门/拟杆菌门比值的丰度，而且调节了前10个属的丰度，包括norank_f__Muribaculaceae、乳杆菌属、肠杆菌属、Turicibacter、粪杆菌属、毛螺菌科_NK4A136_组、未分类的_f___Lachnospiraceae、norank_f__毛螺菌科。AB 23 A显著降低了血清中脂多糖和支链氨基酸的水平，这与肠杆菌和Turicibacter的丰度呈正相关。此外，AB 23 A导致TLR 4、NF-κ B和mTOR的活化显著降低，并上调紧密连接蛋白（包括ZO-1和occludin）的表达。这些结果表明，AB 23 A在HFD喂养的NAFLD小鼠中显示出益生元能力。
Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from Rhizoma alisamatis that has been widely used as a traditional Chinese medicine (TCM). Previous studies have documented the beneficial effect of AB23A on non-alcoholic fatty liver disease (NAFLD), but the functional interactions between gut microbiota and the antiNAFLD effect of AB23A remain unclear. In this study, we investigated the benefits of experimental treatment with AB23A on gut microbiota dysbiosis in NAFLD with an obesity model. C57BL/6J mice were administrated a high-fat diet (HFD) with or without AB23A for 12 weeks. AB23A significantly improved metabolic phenotype in the HFD-fed mice. Moreover, results of 16S rRNA gene-based amplicon sequencing in each group reveled that AB23A not only reduced the abundance of the Firmicutes/Bacteroidaeota ratio and Actinobacteriota/Bacteroidaeota ratio, but regulated the abundance of the top 10 genera, including norank_f__Muribaculaceae, Lactobacillus, Ileibacterium, Turicibacter, Faecalibaculum, the Lachnospiraceae_NK4A136_group, unclassified_f__Lachnospiraceae, and norank_f__Lachnospiraceae. AB23A significantly reduced the serum levels of lipopolysaccharide and branched chain amino acids, which are positively correlated with the abundances of Ileibacterium and Turicibacter. Moreover, AB23A led to remarkable reductions in the activation of TLR4, NF-kappa B, and mTOR, and upregulated the expression of tight junction proteins, including ZO-1 and occludin. These results revealed that AB23A displayed a prebiotic capacity in HFD-fed NAFLD mice.