Trilobatin, a novel natural food additive, exerts a protective effect on acute liver injury. However, whether Trilobatin can protect against alcoholic liver disease (ALD) has not been elucidated. This research is intended to ascertain the impact of Trilobatin on ALD in mice and decipher the potential underlying mechanisms. Lieber–DeCarli liquid alcohol diet was used to induce ALD in mice, followed by administration of Trilobatin (10, 20, 40 mg·kg^–1·d^–1) for 15 days. The results suggested that Trilobatin significantly alleviated ethanol-induced hepatic injury in mice. Furthermore, RNA-Seq analysis revealed that yes-associated protein (YAP) downregulation occurred in the liver after Trilobatin treatment. Mechanistically, Trilobatin directly bound to YAP and hindered its nuclear translocation, which activated the Nrf2 pathway to reduce pro-inflammatory cytokines and oxidative stress. Intriguingly, 16S rDNA analysis results revealed that Trilobatin reshaped the gut microbiota, reducing harmful bacteria and increasing beneficial bacteria. It also enhanced tight junction proteins, defending against damage to the intestinal barrier. These findings not only highlight the microbiota–gut–liver axis and YAP/Nrf2 pathway as crucial potential targets to treat ALD but also reveal that Trilobatin effectively protects against ALD, at least partly, through modulating the microbiota–gut–liver axis and YAP/Nrf2 pathway.

中文翻译：

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Trilobatin 是一种新型天然食品添加剂，可改善小鼠酒精性肝病：微生物群-肠-肝​​轴和 Yap/Nrf2 信号通路的参与


三叶苷是一种新型天然食品添加剂，对急性肝损伤具有保护作用。然而，三叶苷是否可以预防酒精性肝病（ALD）尚未阐明。本研究旨在确定 Trilobatin 对小鼠 ALD 的影响并破译潜在的潜在机制。使用Lieber-DeCarli液体酒精饮食诱导小鼠ALD，然后给予Trilobatin（10、20、40 mg·kg ^–1 ·d ^–1 ）15天。结果表明，三叶苷可显着减轻乙醇引起的小鼠肝损伤。此外，RNA-Seq 分析显示，Trilobatin 治疗后肝脏中出现 yes 相关蛋白 (YAP) 下调。从机制上讲，Trilobatin 直接与 YAP 结合并阻碍其核转位，从而激活 Nrf2 途径以减少促炎细胞因子和氧化应激。有趣的是，16S rDNA 分析结果显示，Trilobatin 重塑了肠道微生物群，减少有害细菌并增加有益细菌。它还增强了紧密连接蛋白，防止肠道屏障受损。这些发现不仅强调了微生物群-肠-肝​​轴和 YAP/Nrf2 通路是治疗 ALD 的重要潜在靶点，而且还揭示了 Trilobatin 可以有效预防 ALD，至少部分是通过调节微生物群-肠-肝​​轴和 YAP/ Nrf2 途径。