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

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines Pub Date : 2025-09-01 DOI:10.1016/S1875-5364(25)60977-0

Huiling Zhou, Mingzhu Han, Miaomiao Nan, Yingrong Leng, Weiming Huang, Shengtao Ye, Lingyi Kong, Wenjun Xu, Hao Zhang

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引用次数: 0

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.

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从山莨菪中提取的异东A−H、仲枞烷和枞烷型二萜类化合物：分离、结构解析和抗胆固醇抑制活性

从lophanthoides （Buch.-Ham）中分离到8个新的二萜类化合物Isodon A−H（1−8）和13个已知的类似物（9−21）。原句：原句：化合物(+)-3/(−)-3、(+)-4/(−)-4和(+)-5/(−)-5被鉴定为三个对映体对。通过高分辨率电喷雾电离质谱（HR-ESI-MS）、一维和二维核磁共振（NMR）光谱、电子圆二色性（ECD）计算和x射线衍射晶体学确定了1 - 8的平面结构和绝对构型。胆固醇7α-羟化酶（Cyp7a1）荧光素酶报告试验显示，化合物1、(+)-4、6、7、12−14和16具有显著的抗胆固醇抑制活性。此外，化合物6在体外和体内通过法内甾体X受体（FXR）相关信号通路显示出抗胆汁淤积作用。这些发现提示了枇杷膏在药物开发中的潜在应用。

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来源期刊

Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY

CiteScore

7.50

自引率

4.30%

发文量

2235

期刊介绍： The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.