Kaempferol and nicotiflorin ameliorated alcohol-induced liver injury in mice by miR-138-5p/SIRT1/FXR and gut microbiota

作者：Jian Ge, Guangmei Li, Zhaowen Chen, Weijia Xu, Xuanhao Lei, Shengnan Zhu · 发表于：Heliyon · 年份：2023 · DOI：10.1016/j.heliyon.2023.e23336 · 被引用次数：25 · 研究领域：Alcohol Consumption and Health Effects、Drug-Induced Hepatotoxicity and Protection、Heme Oxygenase-1 and Carbon Monoxide

Aims: has been validated to be highly effective for treating hepatitis. Kaempferol and nicotiflorin are two highly representative flavonoids, which have exhibit therapeutic effects on liver disease. Therefore, the protective mechanism of kaempferol and nicotiflorin on alcohol-induced liver injury were investigated. Main methods: Forty mice were used in this study. After treatment of Kaempferol and nicotiflorin, serum and liver were collected and used for determination of biochemical indicators, H&E staining, and molecular detection. The interaction of miRNAs from serum extracellular vehicles (EVs) with mRNAs and 16S rRNA sequencing of gut microbiota were also investigated. Key findings: The results showed that kaempferol and nicotiflorins significantly ameliorated alcohol-induced liver damage and observably regulated gut microbiota. Specifically, the levels of malondialdehyde (MDA) and CYP2E1 in the liver significantly reduced, and the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver evidently increased. They also significantly relieved liver oxidative stress and lipid accumulation by suppressing miR-138-5p expression, inversely enhancing deacetylase silencing information regulator 2 related enzyme-1 (SIRT1) levels and then decreasing farnesoid X receptor (FXR) acetylation, which then modulated Nrf2 and SREBP-1c signaling pathways to regulate oxidative stress and lipid metabolism induced by alcohol. Significance: Kaempferol and nicotiflorin reduced al...