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Amelioration of concanavalin A-induced autoimmune hepatitis by magnesium isoglycyrrhizinate through inhibition of CD4+CD25-CD69+ subset proliferation

Authors Yang Q, Wang J, Liu R, Wang Z, Li Y, Zhang Y, Hao X, Huang Y, Xie W, Wei H

Received 15 July 2015

Accepted for publication 13 October 2015

Published 25 January 2016 Volume 2016:10 Pages 443—453

DOI https://doi.org/10.2147/DDDT.S92440

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Wei Duan


Qi Yang,1,* Jianwei Wang,2,* Ran Liu,2 Zhiqiang Wang,1 Yufeng Li,2 Yifan Zhang,1 Xiaohua Hao,2 Yubo Huang,2 Wen Xie,2 Hongshan Wei1,2

1Beijing Ditan Teaching Hospital, Peking University Health Science Center, Beijing, People’s Republic of China; 2Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China

*These authors contributed equally to this work


Abstract: Magnesium isoglycyrrhizinate (MGL) is a new stereoisomer of glycyrrhizic acid, which is clinically used as a hepatoprotective medicine with more potent effects and less side effects than glycyrrhizic acid. This study was designed to evaluate the protective effects and possible mechanism of MGL against concanavalin A (Con A)-induced autoimmune hepatitis. Hepatitis was induced by Con A in C57/6J mice with or without MGL administration; injury score and serum ALT were evaluated. The CD4+ T-cells were isolated from splenocytes and challenged with Con A after coculturing with MGL. The injury score was significantly improved in MGL-treated mice after Con A challenging for 12 and 24 hours compared with those merely challenged with Con A. Similar trends were observed in the serum levels of ALT and AST. The most interesting result was that MGL administration significantly decreased the frequency of CD4+CD25-CD69+ T-cells rather than CD4+CD25+CD69+ T-cells in peripheral blood mononuclear cells, after Con A challenging 12 and 24 hours. Moreover, the serum ALT levels were markedly correlated with the frequency of CD4+CD25-CD69+ cells, but only weakly correlated with CD4+CD25+CD69+ cells in peripheral blood mononuclear cells. More importantly, MGL (5 mg/mL) almost completely eliminated the proliferation of the CD25-CD69+ subset in primary CD4+ T-cells after Con A challenge. Compared with merely Con A-challenged mice, those with MGL administration significantly demonstrated decreased NALP3, NLRP6, and caspase-3 expression, in which the NALP3 and caspase-3 downregulated in a dose-dependent manner. Our results indicate that MGL may have potential as a therapeutic agent in autoimmune hepatitis by ameliorating liver injury. Its molecular mechanism may be involved in inhibiting CD4+CD25-CD69+ subset proliferation and downregulating inflammasome expression in liver tissue.

Keywords: autoimmune hepatitis, drug therapy, concanavalin A, mouse, adaptive immunity, regulatory T-cell

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