Abstract

Glycyrrhizic acid (GA), the major bioactive triterpene glycoside of glycyrrhiza, has been shown to possess a wide range of pharmacological properties, including anti-inflammatory and anti-viral properties. However, few studies have examined the anti-allergic activity and exact mechanism of action of GA. In the present work, the anti-allergic activity and possible mechanisms of action of GA on an immunoglobulin (Ig) E-mediated allergic reaction has been studied using three models of allergic reaction in vivo and in vitro. Active systemic allergic reaction in Balb/c mice showed that GA can suppress the increased level of IL-4 to restore the immune balance of TH1/TH2 cells in a dose-dependent manner. Additionally, GA attenuated significantly the B cells producing allergen-specific IgE and IgG1 partly because of the low levels of TH2 cytokines. Both passive cutaneous anaphylaxis in vivo and an RBL-2H3 cell-based immunological assay in vitro indicated that GA acted as a “mast cell stabilizer”, as it inhibited mast cell degranulation and decreased vascular permeability by inhibiting the expression of Orai1, STIM1 and TRPC1, which blocked extracellular Ca2+ influxes. The current study suggests that GA may serve as an effective anti-allergic agent derived from food for the prevention and treatment of IgE-mediated allergic reaction.

Highlights

  • An allergic condition describes a hypersensitivity disorder in which the immune system reacts to substances in the environment that are normally considered harmless[1]

  • The rectal temperature in the sensitization group decreased by −1.60 ± 0.1 °C compared to the Alum control group, whereas in the 1 mg/kg∙bw glycyrrhizic acid (GA)-treated group, the rectal temperature was only reduced by −0.90 ± 0.1 °C (Fig. 1C)

  • We confirmed that GA had no effect on the depletion of endoplasmic reticulum (ER) calcium store, but can stabilize mast cells by inhibiting the Ca2+ influx due to the lower expression of calcium channel proteins (Orai[1], STIM1 and TRPC1). Natural triterpenoid compounds, such as glycyrrhizic acid (GA), ursolic acid, oleanolic acid and nomilin, exert similar effects on the immune system of Balb/c mice[12], which may be related to the similarities in their chemical structures

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Summary

Introduction

An allergic condition describes a hypersensitivity disorder in which the immune system reacts to substances in the environment that are normally considered harmless[1]. There are no therapies available to cure allergic diseases completely Some medicines, such as anti-histamine drugs (diphenhydramine, chlorpheniramine maleate, terfenadine, etc.), mast cell stabilizers (disodium cromoglycate, sodium hydroxypropylcromate, ketotifen, etc.) and immune suppressors (adrenal cortical hormones, dexamethasone, hydrocortisone, etc.), can only be used to help relieve allergic symptoms and alleviate the suffering of anaphylaxis. GA (10 mg/ kg∙bw) can attenuate the development of carrageenan-induced acute inflammation by preventing the activation of NF-κB and STAT-317 Based upon these observations, we hypothesized that GA might be a contributing factor in the medicinal or nutritional uses of glycyrrhiza for relieving allergic reaction. The present study was designed to investigate the anti-allergic effect of GA and to explore its possible underlying mechanism using active systemic allergic reaction and passive cutaneous anaphylaxis in vivo and an RBL-2H3 cell-based immunological assay in vitro

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