In vivo hepatoprotective activity and the underlying mechanism of chebulinic acid from Terminalia chebula fruit
In vivo hepatoprotective activity and the underlying mechanism of chebulinic acid from Terminalia chebula fruit
复制标题
榄仁果中车布林酸的体内保肝活性及其潜在机制。
DOI：
10.1016/j.phymed.2021.153479
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发表时间：
2021-02-06
期刊：
影响因子：
7.9
通讯作者：
Ma, Chao-Mei
中科院分区：
文献类型：
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作者：
Feng, Xin-Hong;Xu, Hai-Yan;Ma, Chao-Mei
背景：chebula Retz的果实。是传统医学处方中使用最广泛的草药之一，包括肝病处方。在对具有潜在保肝活性的生物活性成分的筛选中，chebula果实的主要化学成分chebullinic acid （CA）显示出较强的保肝活性。目的：探讨CA对肝脏的保护作用及其机制。方法：分别采用过氧化叔丁基氢（t-BHP）、对乙酰氨基酚（APAP）和CCl4对细胞、斑马鱼幼崽和小鼠的肝毒性模型，观察CA对肝脏的保护作用。结果：CA预处理可通过MAPK/Nrf2信号通路阻断ROS的产生，降低LDH水平，增强HO-1和NQO1的表达，从而预防t- bhp诱导的L-02肝细胞损伤。在动物实验中，通过降低ALT、AST和MDA水平，增强SOD活性，改善肝脏组织病理学改变，激活Nrf2/HO-1信号通路，CA对ccl4诱导的小鼠肝损伤具有显著的保护作用。CA代谢成具有DPPH自由基清除活性的乙酰胆酸异构体。在肝脏特异性表达dred RFP的转基因斑马鱼系中，CA降低了10 mM APAP诱导的肝毒性。结论：细胞实验和两种动物模型实验结果一致，全面阐述了CA的保肝作用。
Background: The fruit of Terminalia chebula Retz. is one of the most widely used herbal drug in Traditional medicine prescriptions including those for liver diseases. In the screening of bioactive constituents that have potential hepatoprotective activity, chebulinic acid (CA) which is a major chemical constituent of T. chebula fruit showed potent activity.Purpose: This work was conducted to investigate the hepatoprotective activity and mechanisms of CA.Methods: The hepatoprotective effect of CA was examined on hepatotoxic models of cells, zebrafish larvae and mice caused by tert-butyl hydrogen peroxide (t-BHP), acetaminophen (APAP) and CCl4, respectively.Results: Pretreatment with CA could prevent t-BHP-induced damage in L-02 hepatocytes by blocking the production of ROS, reducing LDH levels and enhancing HO-1 and NQO1 expression via MAPK/Nrf2 signaling pathway. In animal experiments, CA significantly protected mice from CCl4-induced liver injury, as demonstrated by reduced ALT, AST and MDA levels, enhanced SOD activity, improved liver histopathological changes, and the activation of the Nrf2/HO-1 signaling pathway. CA metabolized to chebulic acid isomers with DPPH radical scavenging activity. In a transgenic zebrafish line with liver specific expression of DsRed RFP, CA diminished the hepatotoxicity induced by 10 mM APAP.Conclusion: Experiments in cell and two animal models demonstrated consistent results and comprehensively expounded the hepatoprotective effects of CA.