Three New Clerodane Diterpenoids and Their NLRP3 Inflammasome Activation Inhibitory Activity from Callicarpa arborea Roxb

Chem Biodivers. 2023 Dec;20(12):e202301676. doi: 10.1002/cbdv.202301676. Epub 2023 Nov 27.

Abstract

Three new compounds callicarpenoids A-C (1-3), were isolated from the stems of Callicarpa arborea Roxb together with fifteen known compounds (4-18). The structures of these compounds were elucidated using advanced spectroscopic techniques, including 1D and 2D NMR, UV, IR, HR-ESI-MS, ECD, ORD, and quantum chemical calculations. Compound 3, a rare rearranged diterpenoid with a fused 5/6-ring system demonstrated strong potential as an inhibitor of the NLRP3 inflammasome activation with an IC50 value of 3.153 μM. It effectively reduced GSDMD-NT production, inhibited caspase-1 activation, and suppressed IL-1β secretion, thereby mitigating NLRP3 inflammasome-induced pyroptosis in J774A.1 cells. These findings suggest that compound 3 warrants further research and development as a promising NLRP3 inflammasome inhibitor.

Keywords: Callicarpa; DP4+; NLRP3 inflammasome; clerodane diterpenoids; spectroscopy.

MeSH terms

  • Callicarpa* / chemistry
  • Diterpenes, Clerodane* / pharmacology
  • Inflammasomes
  • Magnetic Resonance Spectroscopy
  • NLR Family, Pyrin Domain-Containing 3 Protein

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Diterpenes, Clerodane