二氢杨梅素通过调节血清脂质、胆汁酸和回肠微生物群组成改善小鼠非酒精性脂肪性肝炎。
Dihydromyricetin ameliorated nonalcoholic steatohepatitis in mice by regulating the composition of serous lipids, bile acids and ileal microflora.
机构信息
Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, 430062, China.
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, China.
出版信息
Lipids Health Dis. 2023 Aug 2;22(1):112. doi: 10.1186/s12944-023-01871-7.
BACKGROUND
Dihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear.
METHODS
After male C57BL/6 mice was fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum alaninea minotransferase, aspartate aminotransferase and liver triglyceride, malonic dialdehyde were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by Liquid Chromatograph-Mass Spectrometry, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing.
RESULTS
The results showed that the significant changes including 29 lipids, 4 BAs (23-nor-deoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid and cholic acid), 2 BA transporters (Mrp2 and Oatp1b2) and 8 GMs between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, the ratio of Firmicutes/Bacteroidota and the abundance of Erysipelotrichaceae, Faecalibacuium, significantly up-regulated 8 lipids and 5 GMs (Verrucomicrobiota, Bacteroidota, Actinobacteria, Akkermansiaceae and Akkermansia).
CONCLUSIONS
The results suggested that DMY may alleviate MCD diet-induced NASH through decreasing the serum levels of toxic BAs which regulated by liver Oatp1b2 and Mrp2, regulating the metabolism of related lipids, and up-regulating intestinal probiotics (Actinobacteria and Verrucomicrobiota at the phylum level; Akkermansiaceae at the family level; Akkermansiaat at the genus level) and inhibiting intestinal harmful bacteria (Firmicutes at the phylum level; Erysipelotrichaceae at the family level; Faecalibaculum at the genus level).
背景
二氢杨梅素（DMY）是一种具有抗非酒精性脂肪性肝炎（NASH）活性的天然黄酮类化合物。然而，DMY 对 NASH 小鼠血清中脂质和胆汁酸（BA）组成以及回肠肠道微生物群（GM）的影响尚不清楚。
方法
雄性 C57BL/6 小鼠给予蛋氨酸和胆碱缺乏（MCD）饮食，同时灌胃给予 DMY（300mg/kg/天）8 周后，用油红 O、苏木精-伊红和 Masson 染色观察肝组织的病理变化，用试剂盒检测血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和肝甘油三酯水平，用液相色谱-质谱法检测血清脂质和 BA 的组成和含量，用 RT-qPCR 检测肝 BA 稳态相关基因的 mRNA 水平，并用 16S rDNA 测序分析回肠微生物多样性。
结果
结果表明，MCD 和 DMY 组之间存在 29 种脂质、4 种 BA（23-去氧胆酸、熊去氧胆酸、7-酮脱氧胆酸和胆酸）、2 种 BA 转运体（Mrp2 和 Oatp1b2）和 8 种 GM 存在显著变化。其中，DMY 治疗显著下调 21 种脂质、上述 4 种 BA，上调 8 种脂质和 5 种 GM（厚壁菌门/拟杆菌门比值和肠杆菌科、粪杆菌属丰度）Firmicutes/Bacteroidota 和丰度显著上调。
结论
结果表明，DMY 可能通过降低由肝 Oatp1b2 和 Mrp2 调节的有毒 BA 的血清水平，调节相关脂质的代谢，上调肠道益生菌（厚壁菌门和拟杆菌门水平的放线菌和疣微菌科；科水平的阿克曼菌科；属水平的阿克曼菌）和抑制肠道有害细菌（厚壁菌门水平的Firmicutes；科水平的肠杆菌科；属水平的粪杆菌属）来缓解 MCD 饮食诱导的 NASH。
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