Anti-proliferative and anti-inflammatory eudesmanolides from the flowers of Sphagneticola trilobata (L.) Pruski

Twenty-six eudesmanolides including six undescribed compounds were isolated from the flowers of Sphagneticola trilobata (L.) Pruski. Their structures were elucidated based on the interpretation of spectroscopic techniques, NMR calculation, and DP4+ analysis. The stereochemistry of (1S,4S,5R,6S,7R,8S,9R,10S,11S)-1,4,8- trihydroxy-6-isobutyryloxy-11-methyleudesman-9,12-olide (1) was demonstrated by single crystal X-ray diffraction. All eudesmanolides were evaluated for their anti-proliferative activities against four human tumor cell lines (HepG2, HeLa, SGC-7901, and MCF-7). 1 alpha,4 beta-Dihydroxy-6 alpha-methacryloxy-8 beta-isobutyryloxyeudesman-9,12-olide (3) and wedelolide B (8) showed pronounced cytotoxic effects against AGS cell line with IC50 values of 1.31 and 0.89 mu M, respectively. Their anti-proliferative activities against AGS cells were exerted through a dose-dependent apoptosis pathway, as verified by cell and nucleus morphological assessment, clone formation assay, and Western blot analysis. Furthermore, 1 alpha,4 beta,8 beta-trihydroxy-6 beta-methacryloxyeudesman-9,12-olide (2) and 1 alpha,4 beta,9 beta- trihydroxy-6 alpha-isobutyryloxy-11 alpha-13-methacryloxyprostatolide (7) performed significant inhibitory effects on lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages with IC50 values of 11.82 and 11.05 mu M, respectively. Moreover, compounds 2 and 7 could block the nuclear translocation of NF-kappa B and reduce the expression of iNOS, COX-2, IL-1 beta, and IL-6 to exert anti-inflammatory effects. This study provides evidence for the utilization of the eudesmanolides from S. trilobata as lead compounds for further research due to their cytotoxic potential.

Automated summary

Twenty-six eudesmanolides, including six undescribed compounds, were isolated from the flowers of Sphagneticola trilobata and their structures were determined using spectroscopic techniques, NMR calculation, and DP4+ analysis. The crystal structure of compound (1) was confirmed using X-ray diffraction. Various eudesmanolides exhibited cytotoxic and anti-inflammatory effects in different assays. Compounds (3) and (8) showed significant cytotoxic effects against AGS cell line, while compounds (2) and (7) exhibited inhibitory effects on nitric oxide production and anti-inflammatory effects in RAW 264.7 macrophages. These findings suggest the potential of eudesmanolides from S. trilobata for further research as lead compounds.