A natural product inhibitor of the NLRP3 inflammasome derived from Glycyrrhiza uralensis for the treatment of inflammatory diseases

The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a pattern recognition receptor complex recognizing invading pathogens and activating caspase-1 to induce maturation of interleukin (IL)-1β, thereby playing a critical role in the regulation of immune responses. Its aberrant activation is pathogenic to inherited issues for example, cryopyrin-associated occasional syndrome, multiple sclerosis, type 2 diabetes, Alzheimer’s disease and atherosclerosis. The root of Glycyrrhiza uralensis (GU) has been used as herbal medicine worldwide for over 4000 years. GU is a well-recognized, natural sweetener and used as a traditional medicine to treat several diseases and symptoms, including diabetes, lung diseases, and coughs. Although the effects of GU on immunity have been reported, its effects on inflammasomes, have not been fully studied yet. In this study, we elucidated the effect of GU on inflammasome activation using primary mouse macrophages. GU inhibited the production of caspase-1(p10) and mature IL-1β induced by NLRP3 inflammasome activation in primary mouse macrophages. Furthermore, GU markedly inhibited diet-induced adipose tissue inflammation and IL-1β and caspase-1 production in white adipose tissue. The results demonstrate that GU inhibits NLRP3 inflammasome activation in macrophages, suggesting that GU is a potential drug candidate for the treatment of NLRP3 inflammasome-associated inflammatory diseases. Acknowledgement This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ01199002)” Rural Development Administration, Republic of Korea.