Immunological validation of the pharmacological and anti‐allergic action of glycyrrhetinic acid from Glycyrrhizae Radix

ABSTRACT Aim Glycyrrhetinic acid (GA) is an important and active metabolite derived from glycyrrhizin (GL) in Glycyrrhizae Radix (GR) that induces anti‐allergic, anti‐inflammatory, anti‐oxidant, anti‐viral, and anti‐microbial effects in vivo. To validate these beneficial actions of GA as an active compound of GR in vivo, we prepared a monoclonal antibody against GA. Methods The monoclonal antibody, mAb6D6, was prepared and evaluated for cross‐reactivity with GA and its analogs using competitive enzyme‐linked immunosorbent assay. Subsequently, mAb6D6 was used to validate the anti‐allergic action of GA, which was orally administered as GL or hot water extracts of GR, in the IgE‐mediated passive cutaneous anaphylaxis model for immediate hypersensitivity and contact hypersensitivity model. Results MAb6D6 specifically identified GA and had no reactivity against other oleanane‐type compounds and endogenous steroids. This antibody could neutralise the anti‐allergic action of GA in both models in which mice were orally treated with GL or extracts of GR after intravenous injection of the antibody. Conclusion MAb6D6 neutralised the activity of GA in vivo. Therefore, it is essential to analyse the role of GA from GR in Kampo medicine and elucidate its mechanism of action.