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

Drug Delivery

Qian Hu¹  Lu-Lu Jia¹  Hua-Zhen Su¹  Shao-Yuan Huang¹  Jing Zhang²  Sheng-Nan Zhu³  Qin-You Tan³  Juan Xiao⁴  Junfei Jin⁵ 

[1] Clinical Pharmacy and Pharmacology Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, PR China;Clinical Pharmacy and Pharmacology Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, PR China;Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, PR China;Clinical Pharmacy and Pharmacology Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, PR China;Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, PR China;China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, PR China;Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, PR China;China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, PR China;Laboratory of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, PR China;China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, PR China;Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, PR Chin;

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

DOI  :  10.1080/10717544.2018.1472676

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY