1. Protective Effect of 18β-Glycyrrhetinic Acid against Triptolide-Induced Hepatotoxicity in Rats
- Author
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Xiao-Jun Zhang, Haiming Chen, Yan-Feng Huang, Ji Lin, Zi-Ren Su, Xiu-Ting Yu, Dandan Luo, Guanghua Yang, Lian Zhou, Lan Wang, Chang Qu, and Zhen-Biao Zhang
- Subjects
0301 basic medicine ,TUNEL assay ,Article Subject ,biology ,Chemistry ,lcsh:Other systems of medicine ,Pharmacology ,Triptolide ,lcsh:RZ201-999 ,biology.organism_classification ,Nuclear translocation ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Complementary and alternative medicine ,Apoptosis ,030220 oncology & carcinogenesis ,Detoxification ,Toxicity ,Glycyrrhiza ,Tripterygium wilfordii ,Research Article - Abstract
Triptolide (TP) is the major active component of Tripterygium wilfordii Hook F (TWHF) and possesses multiple pharmacological effects. However, hepatotoxicity of TP which is one of the toxic properties slows its progression in clinical application. 18β-Glycyrrhetinic acid (GA) is the main bioactive ingredient of Licorice (Glycyrrhiza glabra L.), a herbal medicine famous for its detoxification. This study aims to investigate whether GA possesses protective effect against TP-induced hepatotoxicity in rats. TP interference markedly elevated serum levels of ALT, AST, and ALP, caused evident liver histopathological changes, and elevated hepatic TNF-α, IL-6, IL-1β, and IFN-γ as well as nuclear translocation of NF-κB. TP also significantly elevated liver MDA and declined hepatic activities of SOD, CAT, and GSH-Px. Assay of TUNEL and apoptosis proteins (Bax, Bcl-2, and active caspase-3) showed that TP induced severe hepatocellular apoptosis. In contrast, low-dose GA (50 mg/kg) significantly reversed TP-induced changes above. However, high-dose GA (100 mg/kg) had no such effect. Overall, these findings indicated that low-dose GA but not high-dose GA exhibited a protective effect against TP-induced hepatotoxicity in rats by anti-inflammation, antioxidation, and antiapoptosis, which suggests that the doses of GA/Licorice should be carefully considered when used together with TWHF or TWHF preparations.
- Published
- 2017