Undescribed sesquiterpene-diterpene heterodimers from the fruits of Aphanamixis polystachya selectively modulate inflammatory markers in RAW 264.7 cells

Abstract

Aphanapolystachones A-C (1-3), three undescribed sesquiterpene-diterpene heterodimers, were obtained from the fruits of Aphanamixis polystachya. Their structures and absolute configurations were identified by extensive analysis of HR-ESI-MS, NMR, experimental and TD-DFT calculated ECD spectra. The biosynthetic pathway of them was also proposed, which is produced by key intermolecular Diels-Alder [4 + 2]-cycloaddition reaction between a guaiane sesquiterpene and an acyclic diterpene. Compounds 1-3 inhibited NO production in LPS activated RAW 264.7 cells with the IC₅₀ values of 1.7 ± 0.2, 3.0 ± 0.3, 5.3 ± 0.3 μM, respectively, lower than that of the positive control L-NMMA (31.5 ± 2.6 μM). In addition, compounds 1-3 significantly reduced IL-6 secretion at diluted concentration of 0.4 μM.

Keywords: Anti-inflammatory activity; Aphanamixis polystachya; Aphanapolystachone; Meliaceae; Sesquiterpene-diterpene heterodimer.