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

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-1 beta 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.