Glycyrrhizin, a High-Mobility Group Box 1 Inhibitor, Improves Lipid Metabolism and Suppresses Vascular Inflammation in Apolipoprotein E Knockout Mice

Abstract

Background: High-mobility group box protein 1 (HMGB1) is known to have proinflammatory properties; however, the mechanisms by which HMGB1 influences immune responses during atherosclerosis (AS) development are not well understood. Thus, this study investigated the relationship between HMGB1 and vascular inflammation in Apoe^–/– mice and whether glycyrrhizin (GLY), a small inhibitor of HMGB1, could have atheroprotective effects in AS. Methods: Apoe^–/– mice on a high-fat diet were treated with GLY (50 mg/kg) or vehicle by gavage once daily for 12 weeks, respectively. Results: The GLY group exhibited significantly decreased serum lipid levels, atherosclerotic plaque deposition, and serum HMGB1 levels, as well as an increased Treg/Th17 ratio. The GLY group displayed increased interleukin-10 (IL-10) and IL-2 expression and decreased IL-17A and IL-6 expression. Furthermore, the GA treatment significantly reduced STAT3 phosphorylation in Th17 cells and increased STAT5 phosphorylation in Treg cells. Conclusions: Our findings indicate that the attenuation of atherosclerotic lesions in Apoe^–/– mice by GLY might be associated with the amelioration of lipid metabolism abnormalities, inhibition of HMGB1 expression, and alterations in the Treg/Th17 ratio.