Callicarpins, Two Classes of Rearranged ent-Clerodane Diterpenoids from Callicarpa Plants Blocking NLRP3 Inflammasome-Induced Pyroptosis
Callicarpins, Two Classes of Rearranged ent-Clerodane Diterpenoids from Callicarpa Plants Blocking NLRP3 Inflammasome-Induced Pyroptosis
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DOI：
10.1021/acs.jnatprod.0c00288
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发表时间：
2020-07-24
影响因子：
5.1
通讯作者：
Xiao, Wei-Lie
中科院分区：
文献类型：
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作者：
Pu, De-Bing;Zhang, Xing-Jie;Xiao, Wei-Lie
从南瓜属(Callicarpaarborea)和整脉南瓜(Callicarpaborem)中分离得到两个化合物：一种是具有双环[5.4.0]-十一烷环体系的A-高固形烷骨架化合物A-D(1-4)，另一种是具有5/6-稠合杂环二萜骨架的石蒜素E-G(5-7)。通过红外光谱、X-射线晶体衍射、化学衍生化和电子圆二色谱(ECD)数据确证了它们的结构。提出了这些木兰素可能的生物合成途径。化合物2、3b和6-8对NLRP3炎症体有较强的抑制作用，IC50值在1.4~5.3mU M之间，化合物2通过抑制J774A.1细胞中Casp-1的活化和IL-1β的分泌而显著抑制NLRP3炎症体诱导的下垂。
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 Callicarpaarborea 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 IC50 values from 1.4 to 5.3 mu M, and 2 significantly blocked NLRP3 inflammasome-induced pyroptosis by inhibiting Casp-1 activation and IL-1 beta secretion in J774A.1 cells.