Isodons A-H,seco-abietane and abietane-type diterpenoids from Isod-on lophanthoides:isolation,structural elucidation,and anti-cholestatic activity
摘要Eight new diterpenoids,Isodons A-H(1-8),comprising seco-abietane and abietane-type structures,together with 13 known analogues(9-21),were isolated from Isodon loph-anthoides(Buch.-Ham.ex D.Don)Hara.The compounds(+)-3/(-)-3,(+)-4/(-)-4,and(+)-5/(-)-5 were identified as three enantiomeric pairs.The planar structures and absolute con-figurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),1D & 2D nuclear magnetic resonance(NMR)spectroscopy,elec-tronic circular dichroism(ECD)calculations,and X-ray diffraction crystallography.A choles-terol 7α-hydroxylase(Cyp7a1)luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1,(+)-4,6,7,12-14,and 16.Additionally,compound 6 demon-strated anti-cholestatic effects through the farnesoid X receptor(FXR)-associated signaling pathways in vitro and in vivo.These findings suggest potential applications for Ⅰ.Loph-anthoides in pharmaceutical development.
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