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-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.