Kay Laboratory of Basic Pharmacology and Joint International Research of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China.
Nutrients. 2022 May 9;14(9):1974. doi: 10.3390/nu14091974.
Tratt. fruit juice (Cili) is used as a medicinal and edible resource in China due to its antioxidant and hypolipidemic potentials. The efficacy of Cili in protecting alcohol-induced liver injury and its underlying mechanism was investigated. C57BL/6J mice received a Lieber-DeCarli liquid diet containing alcohol to produce liver injury. After the mice were adapted gradually to 5% alcohol, Cili (4 mL and 8 mL/kg/day for 4 weeks) were gavaged for treatment. The serum enzyme activities, triglyceride levels, histopathology and Oil-red O staining were examined. The RNA-Seq and qPCR analyses were performed to determine the protection mechanisms. Cili decreased serum and liver triglyceride levels in mice receiving alcohol. Hepatocyte degeneration and steatosis were improved by Cili. The RNA-Seq analyses showed Cili brought the alcohol-induced aberrant gene pattern towards normal. The qPCR analysis verified that over-activation of CAR and PXR (Cyp2a4, Cyp2b10 and Abcc4) was attenuated by Cili. Cili alleviated overexpression of oxidative stress responsive genes (Hmox1, Gsta1, Gstm3, Nqo1, Gclc, Vldlr, and Cdkn1a), and rescued alcohol-downregulated metabolism genes (Angptl8, Slc10a2, Ces3b, Serpina12, C6, and Selenbp2). Overall, Cili was effective against chronic alcohol liver injury, and the mechanisms were associated with decreased oxidative stress, improved lipid metabolism through modulating nuclear receptor CAR-, PXR-and Nrf2-mediated pathways.
刺梨（Cili）作为一种具有抗氧化和降血脂潜力的药食两用资源，在中国被用作药材。本研究旨在探究刺梨对酒精性肝损伤的保护作用及其潜在机制。C57BL/6J 小鼠接受含酒精的 Lieber-DeCarli 液体饮食以产生肝损伤。在小鼠逐渐适应 5%酒精后，给予刺梨（4 mL 和 8 mL/kg/天，连续 4 周）灌胃治疗。检测血清酶活性、甘油三酯水平、组织病理学和油红 O 染色。进行 RNA-Seq 和 qPCR 分析以确定保护机制。刺梨降低了接受酒精的小鼠的血清和肝脏甘油三酯水平。刺梨改善了肝细胞变性和脂肪变性。RNA-Seq 分析表明，刺梨使酒精引起的异常基因模式恢复正常。qPCR 分析证实，刺梨减弱了 CAR 和 PXR（Cyp2a4、Cyp2b10 和 Abcc4）的过度激活。刺梨减轻了氧化应激反应基因（Hmox1、Gsta1、Gstm3、Nqo1、Gclc、Vldlr 和 Cdkn1a）的过表达，并挽救了酒精下调的代谢基因（Angptl8、Slc10a2、Ces3b、Serpina12、C6 和 Selenbp2）。总之，刺梨对慢性酒精性肝损伤有效，其机制与降低氧化应激、通过调节核受体 CAR-、PXR-和 Nrf2 介导的途径改善脂质代谢有关。
