Lipid-Lowering Activities of Cucurbitacins Isolated from Trichosanthes cucumeroides and Their Synthetic Derivatives

doi:10.1021/acs.jnatprod.0c00364

	Lipid-Lowering Activities of Cucurbitacins Isolated from Trichosanthes cucumeroides and Their Synthetic Derivatives
	Zhang, Xianjing 1,2; Li, Huihui 1,2; Wang, Wenqiong 1; Chen, Tong 1; Xuan, Lijiang 1,2
刊名	JOURNAL OF NATURAL PRODUCTS
	2020-12-24
卷号	83 期号:12 页码:3536-3544
ISSN号	0163-3864
DOI	10.1021/acs.jnatprod.0c00364
通讯作者	Xuan, Lijiang(ljxuan@simm.ac.cn)
英文摘要	In the ongoing efforts to discover natural cholesterol-lowering compounds, dihydrocucurbitacin B, isolated from Trichosanthes cucumeroides roots, was found to promote LDL uptake by upregulating LDLR protein in a PCSK9-dependent process. In this study, an in-depth investigation of T. cucumeroides roots afforded 27 cucurbitacins (1-27), including seven new cucurbitacins (1-7), and their structures were elucidated by spectroscopic data analyses. In order to gain insight into their structure-activity relationship, cucurbitacin derivatives (B1-11 and DB1-11) were synthesized. Evaluation of lipid-lowering activities of these cucurbitacins by an LDL uptake assay in HepG2 cells revealed that most of the compounds improved the LDL uptake rate, among which hexanorisocucurbitacin D (6) and isocucurbitacin D (21) exhibited the highest activities (rates of 2.53 and 2.47, respectively), which were comparable to that of the positive control, nagilactone B (rate of 2.07). According to a mechanistic study by Western blot analysis, compounds 6 and 21 dosedependently increased LDLR protein levels and reduced PCSK9 protein levels, representing promising new lipid-lowering drug candidates.
资助项目	Personalized Medicines Molecular Signature based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040335] ; National Natural Science Foundation of China[81773863] ; Youth Innovation Promotion Association ; National Science and Technology Major Project[2019ZX09201004-003-041] ; National Science and Technology Major Project[2019ZX09201004-003-042]
WOS关键词	GENE-EXPRESSION ; TRITERPENOIDS
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000603402900006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296145]
专题	中国科学院上海药物研究所
通讯作者	Xuan, Lijiang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xianjing,Li, Huihui,Wang, Wenqiong,et al. Lipid-Lowering Activities of Cucurbitacins Isolated from Trichosanthes cucumeroides and Their Synthetic Derivatives[J]. JOURNAL OF NATURAL PRODUCTS,2020,83(12):3536-3544.
APA	Zhang, Xianjing,Li, Huihui,Wang, Wenqiong,Chen, Tong,&Xuan, Lijiang.(2020).Lipid-Lowering Activities of Cucurbitacins Isolated from Trichosanthes cucumeroides and Their Synthetic Derivatives.JOURNAL OF NATURAL PRODUCTS,83(12),3536-3544.
MLA	Zhang, Xianjing,et al."Lipid-Lowering Activities of Cucurbitacins Isolated from Trichosanthes cucumeroides and Their Synthetic Derivatives".JOURNAL OF NATURAL PRODUCTS 83.12(2020):3536-3544.