Magnesium isoglycyrrhizinate ameliorates concanavalin A-induced liver injury via the p38 and JNK MAPK pathway

Abstract

Context

Acute liver failure is a serious disease caused by a variety of factors, and immunological injury is an important pathological process. Comprehensive liver treatment efficacy is poor, and the mortality rate is high. Magnesium isoglycyrrhizinate (MgIG) is a new glycyrrhizin drug extracted from the traditional Chinese medicine licorice. The mechanism by which MgIG regulates ConcanavalinA (ConA)-induced immunological liver injury in mice is not completely clear.

Materials and methods

Immunological liver injury was induced in mice by ConA injection, and the inflammatory macrophages model was induced by lipopolysaccharide (LPS). MgIG was administered 30 min prior to ConA and LPS treatment. The mice in the different groups were sacrificed 12 h after treatment, and macrophages were measured at 30 min, 1 h, and 2 h after induction. Macrophages, liver, and blood samples were then collected for analysis.

Results

After drug administration, the MgIG group showed a marked decrease in serum transaminase levels, reduced apoptosis and hepatic inflammatory responses compared to the ConA group. Furthermore, there was a significant reduction in inflammatory cytokine levels in the serum and liver tissue. In vitro, the expression of inflammatory cytokines was distinctly reduced after MgIG administration. In addition, MgIG pretreatment reduced the expression of inflammatory cytokines and regulated the phosphorylation of p38 and JNK proteins in the MAPK pathway.

Conclusion

These findings demonstrated that MgIG protects against ConA-induced immunological liver injury by markedly alleviating liver inflammation, and this provides guidance for the clinical amelioration of liver inflammation induced by immunological factors.

Keywords:

• Magnesium isoglycyrrhizinate
• Concanavalin A
• acute liver failure
• inflammation
• mitogen-activated protein kinase pathway

Author contributions

Zhongping D, Yu C and Xiaohui Z designed the experiments; Yudi G performed the experiments and wrote the manuscript; Feng R and Xiangying Z supervised the experiments; Yuan T prepared the samples and collected the data; Yudi G performed the statistical analyses. All authors have read and approved the submission of the manuscript.

Disclosure statement

The authors declare that they have no conflicts of interest with respect to this study.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant no. 81770611]; Tianqing Liver Disease Foundation of CFHPC [Grant no. TQGB20180213]; National Key R&D Program of China [Grant no. 2017YFA0103000]; Beijing Municipal Administration of Hospitals Ascent Plan [Grant no. DFL20151601]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [Grant no. ZYLX201806]; and the National Science and Technology Key Project on Major Infectious Diseases including HIV/AIDS, Viral Hepatitis Prevention and Treatment [Grant nos. 2012ZX10002004-006, 2017ZX10203201-005, 2017ZX10201201-001-001, 2017ZX10201201-002-002, 2017ZX10202203-006-001, 2017ZX10302201-004-002].