251. Licorice root extract and magnesium isoglycyrrhizinate protect against triptolide-induced hepatotoxicity via up-regulation of the Nrf2 pathway
- Author
-
Shao-Yuan Huang, Jing Zhang, Lu-Lu Jia, Junfei Jin, Sheng-Nan Zhu, Qin-You Tan, Juan Xiao, Hua-Zhen Su, and Qian Hu
- Subjects
0301 basic medicine ,Male ,Antioxidant ,medicine.medical_treatment ,Anti-Inflammatory Agents ,Pharmaceutical Science ,Pharmacology ,Plant Roots ,Antioxidants ,chemistry.chemical_compound ,0302 clinical medicine ,Licorice root extract ,Liver injury ,biology ,Chemistry ,Multidrug resistance-associated protein 2 ,MIG ,Nrf2/ARE ,Biological activity ,General Medicine ,Up-Regulation ,Liver ,030220 oncology & carcinogenesis ,Toxicity ,Chemical and Drug Induced Liver Injury ,Diterpenes ,Research Article ,hepatotoxicity ,Drug-Related Side Effects and Adverse Reactions ,NF-E2-Related Factor 2 ,Down-Regulation ,03 medical and health sciences ,In vivo ,medicine ,Glycyrrhiza ,Animals ,Humans ,Rats, Wistar ,L-02 cell ,Plant Extracts ,lcsh:RM1-950 ,Triptolide ,Phenanthrenes ,Saponins ,medicine.disease ,biology.organism_classification ,Triterpenes ,Rats ,Oxidative Stress ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Epoxy Compounds ,Tripterygium wilfordii ,Drugs, Chinese Herbal - 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.
- Published
- 2018