Abstract

The roots and rhizomes of Glycyrrhiza species (licorice) have been widely used as natural sweeteners and herbal medicines. The aim of this study is to investigate the effect of glycyrrhizic acid (GA) from licorice on macrophage polarization. Both phenotypic and functional activities of murine bone marrow-derived macrophages (BMDMs) treated by GA were assessed. Our results showed that GA obviously increased the cell surface expression of CD80, CD86, and MHCII molecules. Meanwhile, GA upregulated the expression of CCR7 and the production of TNF-α, IL-12, IL-6, and NO (the markers of classically activated (M1) macrophages), whereas it downregulated the expression of MR, Ym1, and Arg1 (the markers of alternatively activated (M2) macrophage). The functional tests showed that GA dramatically enhanced the uptake of FITC-dextran and E. coli K88 by BMDMs and decreased the intracellular survival of E. coli K88 and S. typhimurium. Moreover, we demonstrated that JNK and NF-κB activation are required for GA-induced NO and M1-related cytokines production, while ERK1/2 pathway exhibits a regulatory effect via induction of IL-10. Together, these findings indicated that GA promoted polarization of M1 macrophages and enhanced its phagocytosis and bactericidal capacity. The results expanded our knowledge about the role of GA in macrophage polarization.

Highlights

  • Licorice, the root of Glycyrrhiza uralensis, is a wellrecognized, natural sweetener and used as a traditional herbal medicine for the treatment of various pathological conditions, including allergies, liver disease, gastric ulcers, and adrenal insufficiency [1, 2]

  • It has been shown that glycyrrhizic acid (GA) can promote function of endothelial system and secretion of cytokines such as interleukin- (IL-) 1 and interferon- (IFN-) α [9], induce maturation of dendritic cells (DCs) [10], increase T cells proliferation and production of IL-2 and IFN-γ [11, 12], augment natural killer (NK) cell activity [13], enhance phagocytic capacity and nitric oxide (NO) production in activated macrophages [14], and downregulate the production of IL-8 and eotaxin-1 in human lung fibroblast cells [4]

  • We investigated the effect of GA on the polarization of murine bone marrow-derived macrophages (BMDMs) and found that GA promotes M1, rather than M2 macrophage polarization with enhanced phagocytosis and bacterial killing capacity

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Summary

Introduction

The root of Glycyrrhiza uralensis, is a wellrecognized, natural sweetener and used as a traditional herbal medicine for the treatment of various pathological conditions, including allergies, liver disease, gastric ulcers, and adrenal insufficiency [1, 2]. A number of components have been isolated from licorice, including triterpene saponins, flavonoids, polysaccharides, and other substances [3]. Glycyrrhizic acid (GA), a major biologically active constituent of licorice root accounting for the sweet taste, is a triterpene glycoside containing one molecule of 18-glycyrrhetinic acid and two molecules of glucuronic acid [4]. It has been shown that GA can promote function of endothelial system and secretion of cytokines such as interleukin- (IL-) 1 and interferon- (IFN-) α [9], induce maturation of dendritic cells (DCs) [10], increase T cells proliferation and production of IL-2 and IFN-γ [11, 12], augment natural killer (NK) cell activity [13], enhance phagocytic capacity and nitric oxide (NO) production in activated macrophages [14], and downregulate the production of IL-8 and eotaxin-1 in human lung fibroblast cells [4]. These studies indicated that GA may serve as an immune modulator which precisely regulates the cellular immunity

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