Callicarpins, Two Classes of Rearranged ent -Clerodane Diterpenoids from Callicarpa Plants Blocking NLRP3 Inflammasome-Induced Pyroptosis

作者：De-Bing Pu, Xing‐Jie Zhang, De‐Wen Bi, Junbo Gao, Yan Yang, Xiao‐Li Li, Xiao‐Li Li, Jing Lin, Xiao‐Nian Li, Xiao‐Nian Li, Ruihan Zhang, Wei‐Lie Xiao · 发表于：Journal of Natural Products · 年份：2020 · DOI：10.1021/acs.jnatprod.0c00288 · 被引用次数：38 · 研究领域：Natural product bioactivities and synthesis、Toxin Mechanisms and Immunotoxins、Inflammasome and immune disorders

Callicarpins A–D ( 1 – 4 ), possessing an unprecedented A- homoent -clerodane scaffold with a bicyclo[5.4.0]undecane ring system, and callicarpins E–G ( 5 – 7 ), with 5/6-fused ent -clerodane diterpenoid skeletons, were isolated from Callicarpa arborea and C. integerrim . Their structures were elucidated by comprehensive spectroscopic data, X-ray crystal diffraction, chemical derivatization, and electronic circular dichroism (ECD) data. Putative biosynthetic pathways for these callicarpins are proposed. Compounds 2, 3b, and 6 – 8 showed potent inhibitory effects against the NLRP3 inflammasome with IC 50 values from 1.4 to 5.3 μM, and 2 significantly blocked NLRP3 inflammasome-induced pyroptosis by inhibiting Casp-1 activation and IL-1β secretion in J774A.1 cells.