<p>Diammonium Glycyrrhizinate Mitigates Liver Injury Via Inhibiting Proliferation Of NKT Cells And Promoting Proliferation Of Tregs</p>

Abstract

PurposeDiammonium 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.MethodsC57BL/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).ResultsOur 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.ConclusionWe 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.

Immune Cell Landscape in Gastric Cancer

“…Interestingly, in our work, high Treg infiltration portended a more favorable prognosis in GC. This result was consistent with other group studies where the high expression of FOXP3, a specific transcriptional regulator in Tregs, also showed a favorable prognosis [ 22 – 24 ]. In addition, patients who received radiation therapy and targeted molecular therapy always often were accompanied by low Treg infiltration.…”

Effect of nicotinamide riboside on lipid metabolism and gut microflora‐bile acid axis in alcohol‐exposed mice

“…The latter two groups were given ethanol at the same dose as the Model group after intervention treatment for 1 hr, while the other groups were given equivalent normal saline at the same time. Dose levels of NR and diammonium glycyrrhizinate were selected according to previous studies (Gao et al., 2019; Wang et al., 2018). Only one mouse was kept in each cage during the experiment.…”

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“…It is an efficient hepatoprotective medication in patients with chronic hepatitis C (Tanaka et al, 2009) and more broadly to protect from a variety of hepatic diseases such as chronic viral hepatitis, drug-or chemical-induced liver injury, nonalcoholic fatty liver disease, autoimmune hepatitis and hepatocellular carcinoma (Li, Sun, & Liu, 2019). Most of these effects can be attributed to the drug inhibitory activity on inflammatory cytokines in the liver and activation of CD8 + T cells and Tregs proliferation (Gao et al, 2019). One of the main GLRcontaining preparation is intravenous Stronger Neo-Minophagen C (SNMC, from Minophagen Pharmaceutical Co. Ltd., Tokyo) used for suppression of hepatitis activity and prevention of disease progression in patients with hepatitis B virus-and HCV-induced chronic hepatitis.…”