Two new clerodane diterpenoids and their anti-inflammatory activity from <i>Callicarpa integerrima</i>

A phytochemical investigation of <i>Callicarpa integerrima</i> resulted in the isolation of two previously undescribed clerodane diterpenoids, compounds <b>1</b> and <b>2</b>, in addition to four known compounds (<b>3-6</b>). Structural determination of the new compounds was accomplished through a comprehensive investigation of their spectral data (1D and 2D NMR, HR-ESI-MS and UV/IR), and their absolute configurations were assigned by the comparison of the experimental and calculated ECD curves, supported by specific rotation data. LDH release in J774A.1 macrophages was used to evaluate the anti-inflammatory effects of compounds <b>1-6</b>. Compound <b>2</b> revealed remarkable activity, with an IC₅₀ of 5.12 ± 0.24 µM, compared to andrographolide (IC₅₀ of 12.48 ± 0.60 µM), effectively inhibiting lipopolysaccharide and nigericin-induced pyroptosis in a dose-dependent manner, highlighting its potential as a promising NLRP3 inflammasome inhibitor for further development.