Anti-inflammatory effects of glycyrrhizin on lipoteichoic acid and lipopolysaccharide-induced bovine mastitis

Bovine mastitis is primarily treated with antimicrobial agents. Anti-inflammatory agents are also used to alleviate clinical symptoms or reduce antimicrobial use. Glycyrrhizin is an anti-inflammatory agent used in the treatment of bovine mastitis, but its effects are not fully understood. We therefore examined the anti-inflammatory effects of glycyrrhizin both in vivo and in vitro. We first tested whether glycyrrhizin exerts anti-inflammatory effects using MAC-T cells, an immortalized bovine mammary epithelial cell line. Glycyrrhizin decreased the expression of interleukin (IL)-1 beta mRNA in a concentration-dependent manner in MAC-T cells stimulated with lipoteichoic acid (LTA). We then investigated the effects of glycyrrhizin in bovine mammary epithelial cells (bMECs), which seem to retain more of the characteristics of actual mammary epithelial cells. Stimulation with LTA or lipopolysaccharide significantly increased cytokine mRNA expression in bMECs. Glycyrrhizin exhibited a slight inhibitory effect, but no significant difference was observed. The effect of glycyrrhizin on LTA-induced mastitis was examined in lactating cows. Quarters were divided into test and control areas (test quarter: n=8, control quarter: n=7). All quarters were stimulated with LTA at the start of the trial (0 h). In the test quarter group, glycyrrhizin was administered via intramammary infusion. The somatic cell count and relative gene expression of IL-1 beta and tumor necrosis factor-alpha were significantly lower in test quarters than control quarters. Both the in vitro and in vivo studies showed that glycyrrhizin reduces the expression of proinflammatory cytokine genes in response to LTA-induced inflammation and partially revealed the mechanism of the anti-inflammatory effect of glycyrrhizin on mastitis. Further investigations involving field cases of mastitis with bacterial infections are needed to demonstrate the anti-inflammatory effect of glycyrrhizin on bovine mastitis.