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

Abstract

Callicarpins A-D (<b>1</b>-<b>4</b>), possessing an unprecedented A-<i>homoent</i>-clerodane scaffold with a bicyclo[5.4.0]undecane ring system, and callicarpins E-G (<b>5</b>-<b>7</b>), with 5/6-fused <i>ent</i>-clerodane diterpenoid skeletons, were isolated from <i><i>Callicarpa</i>arborea</i> and <i>C. integerrim</i>. 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 <b>2</b>, <b>3b</b>, and <b>6</b>-<b>8</b> showed potent inhibitory effects against the NLRP3 inflammasome with IC₅₀ values from 1.4 to 5.3 μM, and <b>2</b> significantly blocked NLRP3 inflammasome-induced pyroptosis by inhibiting Casp-1 activation and IL-1β secretion in J774A.1 cells.