Diammonium Glycyrrhizinate Mitigates Liver Injury Via Inhibiting Proliferation Of NKT Cells And Promoting Proliferation Of Tregs
Received 19 June 2019
Accepted for publication 24 August 2019
Published 16 October 2019 Volume 2019:13 Pages 3579—3589
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Dr Anastasios Lymperopoulos
Meixin Gao,1,* Xiulan Li,2,* Lingling He,3 Junru Yang,3 Xiaohui Ye,3 Fan Xiao,4 Hongshan Wei1–3
1Department of Gastroenterology, Peking University Ditan Teaching Hospital, Beijing 100015, People’s Republic of China; 2Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People’s Republic of China; 3Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People’s Republic of China; 4Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Hongshan Wei
Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun East Street, Chaoyang District, Beijing 100015, People’s Republic of China
Purpose: Diammonium glycyrrhizinate (DG) is a replacement for glycyrrhizic acid, which is used as a hepatic protector in clinical practice for most liver diseases. The potential role of immune response during autoimmune hepatitis—induced by concanavalin A (Con A)—remains to be elucidated.
Methods: C57BL/6J mice were treated with two different doses of DG (75 and 200 mg/kg) 2 hrs before administering Con A. The mice were sacrificed after administering Con A for 0, 6, and 24 hrs. Liver damage grade and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin levels were evaluated. The expression level of cleaved-caspase 3 in liver was detected by Western blotting. Inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interferon γ (IFN-γ) in liver were detected by RT-PCR. Thymus, peripheral blood, spleen, and liver tissues were collected to analyze the percentages of NKT cells, subsets of CD4+CD25−CD69+ and CD8+CD69+ T cells, and subsets of regulatory T cells (Tregs).
Results: Our results revealed that DG pre-treatment significantly decreased the serum ALT and AST levels and improved the histological damage in Con A-induced autoimmune liver injury. Pre-treatment with DG down-regulated the inflammatory cytokines upon challenge with Con A. The DG pre-treatment inhibited the apoptosis of T lymphocytes in the thymus. Further, it effectively suppressed the proliferation of CD4+CD25−CD69+ and CD8+CD69+ subsets in the peripheral blood and spleen. In addition, the DG pretreatment significantly downregulated the frequency of NKT cells, while upregulating the frequency of Tregs in the liver.
Conclusion: We believe that the potential protective effect of DG against Con A-induced hepatitis may be partially attributed to its inhibitory activities on inflammatory cytokines in the livers, lymphocyte apoptosis in the thymus, NKT cells proliferation, and activation of CD8+T cells; further, there may also be a possibility of DC promoting Tregs proliferation.
Keywords: autoimmune hepatitis, concanavalin A, diammonium glycyrrhizinate, NKT cells, regulatory T-cell
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