BK21plus team, College of Pharmacy, The Catholic University of Korea, Bucheon, Korea.
Departments of Dermatology, Venereology, Allergology, and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau, Germany.
Phytother Res. 2018 Dec;32(12):2551-2559. doi: 10.1002/ptr.6195. Epub 2018 Oct 3.
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.
痤疮丙酸杆菌（P. acnes）激活 NACHT、LRR 和 PYD 结构域包含蛋白 3（NLRP3）炎症小体对于诱导炎症和加重痤疮病变的发展至关重要。我们寻找了可用于治疗痤疮的 NLRP3 炎症小体的小分子抑制剂。我们发现，从甘草根中分离出的查尔酮类化合物甘草查尔酮 A 是一种有效的 P. acnes 诱导的 NLRP3 炎症小体激活抑制剂。甘草查尔酮 A 阻断了 P. acnes 诱导的原代小鼠巨噬细胞和人 SZ95 皮脂腺细胞中半胱氨酸蛋白酶-1（p10）和白细胞介素-1β的产生，表明它抑制了 NLRP3 炎症小体。甘草查尔酮 A 抑制了 P. acnes 诱导的 ASC 斑点形成和线粒体活性氧的产生。甘草查尔酮 A 局部应用于小鼠耳部皮肤，通过组织学评估、耳部厚度测量和炎症基因表达，减轻了 P. acnes 诱导的皮肤炎症。甘草查尔酮 A 降低了 P. acnes 注射小鼠耳部的半胱氨酸蛋白酶-1 活性和白细胞介素-1β的产生。这项研究表明，甘草查尔酮 A 作为 NLRP3 炎症小体的有效抑制剂，在控制 P. acnes 诱导的皮肤炎症方面是有效的。我们的研究为通过靶向 NLRP3 炎症小体开发抗痤疮治疗提供了新的范例。
