Glycyrrhizic Acid and 18β-Glycyrrhetinic Acid Inhibit Inflammation via PI3K/Akt/GSK3β Signaling and Glucocorticoid Receptor Activation

Many lung-related diseases, such as asthma and chronic obstructive pulmonary disease, are initiated by airway inflammation, and several studies indicate that glycyrrhizic acid (GA) alleviates inflammatory lung disease. We previously showed that GA and 18beta-glycyrrhetinic acid (18betaGA), found in licorice, can act as neuroprotective agents by promoting downstream PI3K/Akt signaling. In this study, we investigate the effects of GA and 18betaGA on inflammation. We show that both GA and 18betaGA reduce inflammatory cytokine production and its resulting anti-inflammation. GA acts via PI3K/Akt/GSK3beta to reduce cytokine production, while 18betaGA leads to the dissociation of a glucocorticoid receptor (GR)-HSP90 complex to block inflammation. Our data suggest that GA and 18betaGA display anti-inflammatory activities but inhibit inflammation via different mechanisms. We propose that GA and 18betaGA may be valuable biological inhibitors of lung inflammation. Interestingly, these data may explain why licorice is frequently used to treat inflammatory disease and it might be a promising nutraceutical for remedying inflammation.