Isodons A-H, seco-abietane and abietane-type diterpenoids from Isodon lophanthoides: isolation, structural elucidation, and anti-cholestatic activity.
10.1016/S1875-5364(25)60977-0
- Author:
Huiling ZHOU
1
;
Mingzhu HAN
1
;
Miaomiao NAN
1
;
Yingrong LENG
1
;
Weiming HUANG
1
;
Shengtao YE
1
;
Lingyi KONG
2
,
3
;
Wenjun XU
4
;
Hao ZHANG
5
Author Information
1. State Key Laboratory of Natural Medicines, Joint International Research Laboratory of Target Discovery and New Drug Innovation (Ministry of Education), School of Traditional Chinese Pharmacy, Affiliated Jiangning Chinese Medicine Hospital, China Pharmaceutical University, Nanjing 210009, China.
2. State Key Laboratory of Natural Medicines, Joint International Research Laboratory of Target Discovery and New Drug Innovation (Ministry of Education), School of Traditional Chinese Pharmacy, Affiliated Jiangning Chinese Medicine Hospital, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpu_lykong@
3. com.
4. State Key Laboratory of Natural Medicines, Joint International Research Laboratory of Target Discovery and New Drug Innovation (Ministry of Education), School of Traditional Chinese Pharmacy, Affiliated Jiangning Chinese Medicine Hospital, China Pharmaceutical University, Nanjing 210009, China. Electronic address: wjxu@cpu.edu.cn.
5. State Key Laboratory of Natural Medicines, Joint International Research Laboratory of Target Discovery and New Drug Innovation (Ministry of Education), School of Traditional Chinese Pharmacy, Affiliated Jiangning Chinese Medicine Hospital, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zhanghao@cpu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Anticholestatic effect;
Cyp7a1;
Diterpenoids;
FXR;
Isodon lophanthoides
- MeSH:
Abietanes/pharmacology*;
Molecular Structure;
Animals;
Isodon/chemistry*;
Humans;
Diterpenes/pharmacology*;
Plant Extracts/chemistry*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(9):1133-1142
- CountryChina
- Language:English
-
Abstract:
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.
