Bioassay and NMR-HSQC-Guided Isolation and Identification of Phthalide Dimers with Anti-Inflammatory Activity from the Rhizomes of Angelica sinensis

Abstract

Under the guidance of a bioactivity-guided approach and HSQC characteristic signals, nine pairs of phthalic dimers, angesilides A–I (1–9), with complex polycyclic skeletons featuring bridged, fused, and spiro ring systems were discovered from the rhizomes of Angelica sinensis. Their structures and absolute configurations were established by comprehensive spectroscopic methods, X-ray diffraction analysis, and chiral separation. Plausible biosynthetic pathway for 1–9 was proposed. Moreover, the anti-inflammatory activities of all isolates were evaluated in lipopolysaccharide (LPS) stimulated mouse leukemia cells of monocyte macrophages (RAW = 264.7). Among them, compound 9 showed a remarkable inhibitory activity with IC₅₀ values of 425 nM and could significantly decrease IL-1β and IL-6 transcription levels. Interestingly, (+)-9 has superior NO inhibitory activity compared to that of (−)-9, which was verified by further molecular docking analysis. The findings provide new insights into A. sinensis as a functional food or for the development of new anti-inflammatory drug candidates.