Jatrophane diterpenoids from Euphorbia helioscopia and their lipid-lowering activities

被引：19

作者：

Li, Jun ^{[1
,3
]}

Li, Hui-hui ^{[2
,3
]}

Wang, Wen-qiong ^{[1
]}

Song, Wei-bin ^{[1
]}

Wang, Yi-ping ^{[2
]}

Xuan, Li-jiang ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China

[3] Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China

来源：

FITOTERAPIA | 2018年 / 128卷

基金：

中国国家自然科学基金;

关键词：

Euphorbia helioscopia; Jatrophanes; Hyperlipidemia; Lipid-lowering; LDL receptor; RECEPTOR MESSENGER-RNA; MODULATORS; ATHEROSCLEROSIS; HYPERLIPIDEMIA; STABILIZATION;

D O I：

10.1016/j.fitote.2018.05.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The phytochemical study of Euphorbia helioscopia led to the isolation of 33 jatrophane diterpenoids (1-33), of which six (1-6) were new. This small jatrophane library was established to screen for potential lipid modulators. LDL-Uptake screening assay demonstrated that most of them improved LDL-Uptake rate in HepG2 cells, with compounds 16, 21 and 26 exhibiting more outstanding effects. Further exploration found that these three compounds could increase LDLR protein level in HepG2 cells dose-dependently. SAR studies suggested that substituted patterns of C-9, steric hindrance between C-14 and C-15, and the long conjugated fragment from C-5 to the carbonyl (C-9) were essential for the activity. Moreover, compound 21, a relatively abundant chemical in E. helioscopia, showed remarkable lipid-lowering effect in vivo, which makes it a promising lead for development of new lipid-lowering agents.

引用

页码：102 / 111

页数：10

共 24 条

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