18β-Glycyrrhetinic acid fromlicorice rootimpairs dendritic cells maturation and Th1 immune responses

Abstract

18β-Glycyrrhetinic acid (β-GA) is a natural triterpenoid compound derived from licorice root. β-GA has been demonstrated to exert antiviral and antitumor effects. However, the effects of the maturation and immunostimulatory functions of dendritic cells (DCs) remain to be clearly elucidated. In this study, we attempted to determine whether β-GA could influence DCs surface molecule expression, antigen uptake capacity, cytokine production and capacity to induce T-cell differentiation. The DCs used in this study were derived from murine bone marrow cells, and were used as immature or lipopolysaccharide (LPS)-stimulated mature DCs. The DCs were then assessed with regard to surface molecules expression, cytokine production, capacity to induce T-cell differentiation and proliferation. β-GA was shown to significantly suppress the expression of surface molecules CD80, CD86, major histocompatibility complex (MHC) class I and MHC class II as well as the levels of interleukin-12 production in LPS-stimulated DCs. Moreover, β-GA-treated DCs showed an impaired induction of the T helper type 1 immune response. These findings provide important understanding of the immunopharmacological functions of β-GA and have ramifications for the development of therapeutic adjuvants for the treatment of DCs-related acute and chronic diseases.

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

“…Glycyrrhizin has been shown to increase activity of dendritic cells, enhance proliferation of allogenic T cells along with production of interferon (IFN)-γ and interleukin (IL)-10 cytokines, and reduce IL-4 production (Bordbar et al, 2012). In contrast, Kim et al (2013c) showed that 18β-glycyrrhetinic acid impaired the capacity of dendritic cells to proliferate and initiate the T helper 1 response in lipopolysaccharide (LPS)-stimulated mature dendritic cells. This compound also suppressed the expression of surface molecules CD80, CD86, and major histocompatibility complex classes I and II and reduced levels of IL-12 production (Kim et al, 2013c).…”

“…In contrast, Kim et al (2013c) showed that 18β-glycyrrhetinic acid impaired the capacity of dendritic cells to proliferate and initiate the T helper 1 response in lipopolysaccharide (LPS)-stimulated mature dendritic cells. This compound also suppressed the expression of surface molecules CD80, CD86, and major histocompatibility complex classes I and II and reduced levels of IL-12 production (Kim et al, 2013c).…”

Plant Components for Immune Modulation Targeting Dendritic Cells: Implication for Therapy

“…Also, the levels of IL-12 production in LPS-stimulated DCs were reduced. In addition, 18β-glycyrrhetinic acid-treated DCs displayed an impaired promotion of Th1 immune response [69]. Previously, the glycyrrhizin, an aqueous extract of licorice root was shown to increase the secretion of IL-10 by liver DCs in mice with hepatitis.…”

“…Polysaccharide GLPs have immunomodulatory, antiangiogenic and cytotoxic activities by affecting the immune cells and immune-related cells including B lymphocytes, T lymphocytes, dendritic cells, macrophages and NK cells [65] Purified GLPs can induce the maturation of murine DCs [66] Antitumor GLPs shows the immunomodulatory, antiangiogenic and cytotoxic activity by affecting the immune cells and immunerelated cells including B lymphocytes, T lymphocytes, DCs, macrophages and NK cells It can induce the production of TNF-α, IL-10, and TGF-β, CD14 + monocyte subpopulation within the PBMCs as well as IL-10 and IL-12 in monocyte-derived dendritic cells [67] Licorice root Osha root, chuchupate, bear medicine, Porter's licorice root A triterpenoid (18β-lycyrrhetinic acid), an aqueous extract of licorice root (glycyrrhizin) Glycyrrhizin increases IL-10 levels by liver dendritic cells in mice with hepatitis [68] 18β-glycyrrhetinic acid could suppress the expression of surface molecules such as CD80, CD86, MHC class I and MHC class II as well as the levels of IL-12 production in polysaccharide-stimulated DCs [69] Antiviral, Antitumor and antiinflammation Glycyrrhizin increases IL-10 levels via liver DCs in mice with hepatitis [70]. For the first time, Bose and his coworkers proposed the antitumor function of NLGP according to its influence on DCs.…”

Synthesis of organoarsenic, organoantimony, and organobismuth poly(ether esters) from reaction with glycyrrhetinic acid and their preliminary activity against pancreatic cancer cell lines

“…GA has also been reported to exhibit antiviral activity against a variety of viruses, including herpes simplex virus and varicella zoster virus. [48][49][50][51][52][53][54][55][56] Recent evidence is that GA can delay the development of the autoimmune disease [57] and decrease body fat. [58] Because it is a potent inducer of mitochondrial permeability transition, it can also trigger the pro-apoptotic pathway.…”