Differential Induction of Isolated Lymphoid Follicles in the Gut by 18β-Glycyrrhetinic Acid

Abstract

18β-glycyrrhetinic acid (GRA) is a pharmacologically active component of licorice root with documented immunomodulatory properties. We reported that GRA administered orally to mice induces B cell recruitment to isolated lymphoid follicles (ILF) in the small intestine and shortens the duration of rotavirus antigen shedding. ILF are dynamic lymphoid tissues in the gut acquired post-natally upon colonization with commensal bacteria and mature through B cell recruitment to the follicles, resulting in up-regulation of IgA synthesis in response to changes in the composition of microbiota. In this study, we investigated potential mechanisms by which GRA induces ILF maturation in the ileum and the colon using mice depleted of enteric bacteria and a select group of mice genetically deficient in pattern recognition receptors. The data show GRA was unable to induce ILF maturation in ileums of mice devoid of commensal bacteria, MyD88−/− or NOD2−/− mice, but differentially induced ILF in colons. Increased expression of chemokine and chemokine receptor genes that modulate B and T cell recruitment to the mucosa were in part dependent on NOD2, TLR, and signaling adaptor protein MyD88. Together the results suggest GRA induces ILF through cooperative signals provided by bacterial ligands under normal conditions to induce B cell recruitment to ILF to the gut, but that the relative contribution of these signals differ between ileum and colon.

The potential of glycyrrhizin and licorice extract in combating COVID-19 and associated conditions

“…18β-glycyrrhetinic acid reduced the duration of viral antigen shedding and increases the serum antibody titers in 18β-glycyrrhetinic acid-treated animals ( Hendricks et al, 2012 ). The mechanism of lymphoid follicles induction by 18β-glycyrrhetinic acid in the gut may through the increase of chemokine and chemokine receptor genes expression that modulates B and T cell recruitment to lymphoid follicles ( Hendricks et al 2014 ). Glycyrrhizin attenuates Salmonella enterica Serovar Typhimurium infection in mice by promoting the release of immune factors ( Xu et al, 2018 ).…”