Biomed Pharmacother. 2019 Feb ;110:692-699. Epub 2018 Dec 12. PMID: 30553196
Glycyrrhizin alleviates Con A-induced hepatitis by differentially regulating the production of IL-17 and IL-25.
Glycyrrhizin, a triterpenoid compound, has been reported to be an anti-inflammatory agent for the treatment of a variety of inflammatory diseases including hepatitis. However, the mechanism by which glycyrrhizin inhibits inflammation is unclear. Using a Con A-induced hepatitis model in mice, we found that administration of glycyrrhizin ameliorates Con A-induced liver injury, which manifests as reduction in the production of inflammatory cytokines IFN-γ, IL-6 and IL-17, as well as serum alanine aminotransferase (ALT). Blockade of IL-17 dramatically mitigates liver injury resulting from Con A challenge. Interestingly, at both the mRNA and protein levels, the endogenous alarmin inflammatory molecule high-mobility group box 1 (HMGB1) is significantly decreased in mice injected with glycyrrhizin combined with Con A compared to those injected with Con A alone. In contrast, the administration of glycyrrhizin with Con A challenge up-regulates the production of IL-25. Furthermore, an increase in the proportion of protective lymphocyte subset, Gr-1CD11b(Myeloid-Derived Suppressor Cell, MDSCs), could be induced by increased IL-25 to restrain immune cell activation and favor the resolution of detrimental immune reactions caused by Con A challenge. The results indicate that glycyrrhizin plays a protective role in Con A-induced hepatitis. This protective role is particularly associated with reducing the production of IL-17 and enhancing the expression of IL-25. The present study may provide a new strategy for the treatment of acute hepatitis in the clinical setting.