LAUSR

Activation of the NACHT, LRR and PYD domains‐containing protein 3 (NLRP3) inflammasome by Propionibacterium acnes (P. acnes) is critical for inducing inflammation and aggravating the development of acne lesions. We searched for available small‐molecule inhibitors of the NLRP3 inflammasome that could be topically administered for the treatment of acne. We found that licochalcone A, a chalconoid isolated from the root of Glycyrrhiza inflate, was an effective inhibitor for P. acnes‐induced NLRP3 inflammasome activation. Licochalcone A blocked P. acnes‐induced production of caspase‐1(p10) and IL‐1β in primary mouse macrophages and human SZ95 sebocytes, indicating the suppression of NLRP3 inflammasome. Licochalcone A suppressed P. acnes‐induced ASC speck formation and mitochondrial reactive oxygen species. Topical application of licochalcone A to mouse ear skin attenuated P. acnes‐induced skin inflammation as shown by histological assessment, ear thickness measurement, and inflammatory gene expression. Licochalcone A reduced caspase‐1 activity and IL‐1β production in mouse ear injected with P. acnes. This study demonstrated that licochalcone A is effective in the control of P. acnes‐induced skin inflammation as an efficient inhibitor for NLRP3 inflammasome. Our study provides a new paradigm for the development of anti‐acne therapy via targeting NLRP3 inflammasome.