期刊
PHYTOMEDICINE
卷 83, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2021.153479
关键词
Chebulinic acid; Hepatoprotective activity; Nrf2; Terminalia chebula
资金
- National Natural Science Foundation of China [81660711]
- Science and Technology Major Project of Inner Mongolia Autonomous Region of China
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock [ZDZX2018065]
Chebulinic acid (CA), a major chemical constituent of Terminalia chebula fruit, has shown potent hepatoprotective effects in cell, zebrafish, and mouse models by regulating the MAPK/Nrf2 signaling pathway.
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.
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