Isodons A-H, seco-abietane and abietane-type diterpenoids from Isodon lophanthoides: isolation, structural elucidation, and anticholestatic activity

Isodons A-H (1−8), 11 new seco-abietane and abietane-type diterpenoids, along with 13 known analogues (9−21), were obtained from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. Compounds ( + )-3/(−)-3, ( + )-4/(−)-4, and ( + )-5/(−)-5 were three pairs of enantiomers. HRESIMS, 1D & 2D NMR, ECD calculations, and X-ray diffraction crystallography data confirmed the planar structures and absolute configurations of 1−8. Cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay showed that compounds 1, ( + )-4, 6, 7, 12−14, and 16 displayed potent anticholestatic activities. Moreover, compound 6 exerted anticholestatic effect via the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These results provided an important reference value for the new application of I. Lophanthoides in medical industry.