Lindenane sesquiterpenoid dimers from Chloranthus japonicus improve LDL uptake by regulating PCSK9 and LDLR

被引：6

作者：

Guo, Pengju ^{[1
,2
]}

Chen, Tong ^{[2
,3
]}

Hu, Xianggang ^{[2
,3
]}

Duan, Yelin ^{[2
,3
]}

Zheng, Liu ^{[2
]}

Du, Gaoxiang ^{[2
,3
]}

Wang, Qing ^{[2
,3
]}

Ding, Aoxue ^{[2
]}

Qin, Guoqing ^{[2
]}

Chen, Yihan ^{[2
,3
]}

Wang, Wenqiong ^{[2
]}

Mu, Qing ^{[1
,2
]}

Xuan, Lijiang ^{[2
,3
]}

机构：

[1] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China

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

[3] Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210029, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2024年 / 142卷

关键词：

Chloranthus japonicas; Lindenane sesquiterpenoid dimers; PCSK9; LDLR; CHEMICAL-CONSTITUENTS; C-F; PLANTS; ROOTS; CHLORAHOLOLIDE; BLOCKERS; POTENT;

D O I：

10.1016/j.bioorg.2023.106958

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

UPLC-TOF-MS/MDF directed phytochemical research of Chloranthus japonicus led to the isolation of 46 lindenane sesquiterpenoid dimers, which included 13 new analogs. Their structures with absolute configurations were elucidated by analysis of spectroscopic data. Fourteen compounds with ester chains significantly decreased PCSK9 protein level in medium of HepG2 cells, especially for compounds 14 and 29 (5 mu M) with inhibition rates of 69.0% and 72.8%, respectively. Compound 14 in HepG2 cells was evaluated via DiI-LDL uptake assays and found to increase LDL uptake by upregulating LDLR mRNA and protein level. Meanwhile, 14 decreased the secretion of PCSK9 protein in medium and downregulated intracellular PCSK9 protein and mRNA level. The discovery of these natural small molecule compounds provides a novel structure basis for design PCSK9 regulators, making them a promising lead for development of new lipid-lowering agents.

引用

页数：13

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