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Drug Deliv. 2018 Nov;25(1):1213-1223. doi: 10.1080/10717544.2018.1472676.

Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide-induced hepatotoxicity via up-regulation of the Nrf2 pathway.

Tan QY1,2,3, Hu Q1, Zhu SN1,2,3, Jia LL1, Xiao J2,3, Su HZ1, Huang SY1, Zhang J1,2, Jin J2,3,4.

Author information

1
a Clinical Pharmacy and Pharmacology Research Institute , The Affiliated Hospital of Guilin Medical University , Guilin , PR China.
2
b Laboratory of Hepatobiliary and Pancreatic Surgery , The Affiliated Hospital of Guilin Medical University , Guilin , PR China.
3
c China-USA Lipids in Health and Disease Research Center , Guilin Medical University , Guilin , PR China.
4
d Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair , Guilin Medical University , Guilin , PR China.

Abstract

Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury. The aim of this study was to investigate the role of the factor erythroid 2-related factor 2 pathway in the protective effects of LE and MIG against triptolide-induced hepatotoxicity. Hepatotoxicity models were established in L-02 cells and rats using triptolide, and the protective effects of LE and MIG were investigated in vitro and in vivo, respectively. LE and MIG significantly protected against triptolide-induced cytotoxicity. Additionally, triptolide decreased the mRNA and protein levels of Nrf2 and down-regulated Nrf2 target genes, including UGT1A, BSEP, and MRP2, while pretreatment with LE and MIG reversed these effects. Finally, Nrf2-involved antioxidant responses were activated in the presence of LE and MIG.

KEYWORDS:

L-02 cell; Licorice root extract; MIG; Nrf2/ARE; hepatotoxicity

PMID:
29791258
PMCID:
PMC6058668
DOI:
10.1080/10717544.2018.1472676
[Indexed for MEDLINE]
Free PMC Article

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