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

作者：Huiling Zhou, Mingzhu Han, Miao-Miao Nan, Yingrong Leng, Weiming Huang, Shengtao Ye, Ling‐Yi Kong, Wen‐Jun Xu, Hao Zhang · 发表于：Chinese Journal of Natural Medicines · 年份：2025 · DOI：10.1016/s1875-5364(25)60977-0 · 研究领域：Bioactive Natural Diterpenoids Research、Plant-based Medicinal Research、Biological Activity of Diterpenoids and Biflavonoids

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 lophanthoides (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 configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.