Abstract
Glycyrrhizin (GL), a triterpenoid glycoside, serves important functions in various biological activities, including antiviral and antitumor immune responses. However, the anti-inflammatory effects of GL on Salmonella enterica serovar Typhimurium (ST)-induced injury in mice and the mechanisms underlying the protection of GL are poorly understood. Here, we investigated the effects of GL on host immune responses against ST infection in mice. A phenotypic analysis using hematoxylin and eosin (H&E) staining and transmission electron microscopy showed that GL relieved ST-induced weight loss and intestinal mucosal injury. A colonization assay showed that GL significantly reduced ST colonization in the ileum and colon and translocation to the liver and spleen. An antibacterial activity assay and real-time PCR revealed that GL had no direct inhibitory impact on ST growth or virulence gene expression. ELISA showed that GL pretreatment significantly decreased proinflammatory cytokine (IFN-γ, TNF-α, IL-6) secretion and increased anti-inflammatory cytokine (IL-10) secretion in the ileum, colon and serum of ST-infected mice. Moreover, flora analysis showed that GL reduced Akkermansia, Sutterella, Prevotella and Coprococcus but enriched Parabacteroides and Anaerotruncus in the cecum of ST-infected mice. These results suggest that GL promotes the secretion of immune factors and modulates intestinal flora to prevent further ST infection. We also analyzed the effect of GL on immunocytes and found that GL promoted the phenotypic and functional maturation of murine bone marrow-derived dendritic cells (BMDCs). Flow cytometry and western blotting demonstrated that NF-κB, ERK, and p38 MAPK were required for GL-induced BMDC maturation. The above findings indicate that GL attenuates ST infection by modulating immune function and intestinal flora. This study enriches our current knowledge of GL-mediated immunological function and provides a new perspective on the prevention of Salmonella infection in animals and humans.
Highlights
Glycyrrhizin (GL), a triterpenoid glycoside, is the major biologically active component of licorice [1]
These results suggest that GL can effectively reduce the weight loss of mice infected with Salmonella
We found that GL could relieve serovar Typhimurium (ST)-induced weight loss and intestinal mucosal injury by hematoxylin and eosin (H&E) staining and SEM examination
Summary
Glycyrrhizin (GL), a triterpenoid glycoside, is the major biologically active component of licorice [1]. Previous studies have reported that GL has important functions in various biological activities, such as immune regulation, apoptosis, oxidative stress, autophagy, tissue regeneration and cell proliferation [2,3,4,5,6]. Accumulating evidence suggests that GL and its metabolite play an important role in antibacterial activities [7,8,9]. GL metabolite has bactericidal activity against penicillin-resistant Staphylococcus aureus and inhibits the expression of virulence genes [11]. Deglycyrrhizinated licorice root extracts (DG-LRE) significantly inhibited biofilm formation by S. mutants UA159 [12]
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