Reviews
Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses
Jie Liu
Yuan‐Fu Lu
Qin Wu
Shang‐Fu Xu
Fu‐Guo Shi
Curtis D. Klaassen
First published: 06 August 2018 https://doi.org/10.1111/liv.13940
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.13940
Abstract
Oleanolic acid (OA) is a triterpenoid that exists widely in fruits, vegetables, and medicinal herbs. OA is included in some dietary supplements and is used as a complementary and alternative medicine (CAM) in China, India, Asia, the US and European countries. OA is effective in protecting against various hepatotoxicants, and one of the protective mechanisms is reprograming the liver to activate the nuclear factor erythroid 2‐related factor 2 (Nrf2). OA derivatives, such as CDDO‐Im and CDDO‐Me, are even more potent Nrf2 activators. OA has recently been shown to also activate the Takeda G‐protein coupled receptor (TGR5). However, whereas a low dose of OA is hepatoprotective, higher doses and long‐term use of OA can produce liver injury, characterized by cholestasis. This paradoxical hepatotoxic effect occurs not only for OA, but also for other OA‐type triterpenoids. Dose and length of time of OA exposure differentiate the ability of OA to produce hepatoprotection versus hepatotoxicity. Hepatotoxicity produced by herbs is increasingly recognized and is of global concern. Given the appealing nature of OA in dietary supplements and its use as an alternative medicine around the world, as well as the development of OA derivatives (CDDO‐Im and CDDO‐Me) as therapeutics, it is important to understand not only that they program the liver to protect against hepatotoxic chemicals, but also how they produce hepatotoxicity.
This article is protected by copyright. All rights reserved. 作者: StephenW 时间: 2018-8-9 11:36