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Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9

文献类型：期刊论文

作者Li, Huihui2,3; Li, Jun2,3; Zhang, Xianjing2,3; Li, Jiaomeng2,3; Xi, Cong2,3; Wang, Wenqiong2,3; Lu, Youli1,4; Xuan, Lijiang2,3
刊名EXPERIMENTAL AND THERAPEUTIC MEDICINE
出版日期2021-12-01
卷号22期号:6页码:9
关键词euphornin L lipid-lowering activity low density lipoprotein receptor proprotein convertase subtilisin kexin type 9 extracellular signal-regulated kinase protein secretion
ISSN号1792-0981
DOI10.3892/etm.2021.10817
通讯作者Xuan, Lijiang(ljxuan@simm.ac.cn)
英文摘要Our previous study identified euphornin L as an active lipid-lowering compound in high-fat diet-fed Golden Syrian hamsters. The aim of the present study was to investigate the mechanisms underlying the lipid-lowering effects of euphornin L. Euphornin L in HepG2 cells was assessed via DiI-LDL update assays and found to increase LDL-update and LDLR protein levels. RNA interference assays demonstrated that its LDL-update effects were LDLR-dependent. Dual luciferase reporter and mRNA stability assays revealed that euphornin L had little effect on LDLR mRNA transcription but lengthened the half-life of LDLR mRNA by activating ERK protein in cells. Euphornin L decreased the secretion of PCSK9 protein and alleviated PCSK9-mediated LDLR protein degradation. In vivo experiments in hamsters, which were treated with euphornin L (30 mg/kg/day) for 3 weeks, confirmed these findings. LDLR protein levels in liver tissue were upregulated, while PCSK9 protein levels in serum were downregulated. Altogether, the present study demonstrated that euphornin L increased LDLR protein levels by dual regulation of LDLR mRNA and PCSK9 protein, and represented an active compound for lipid-lowering drug development.
WOS关键词LOW-DENSITY-LIPOPROTEIN ; RECEPTOR MESSENGER-RNA ; GENE-EXPRESSION ; CHOLESTEROL ; DEGRADATION ; BERBERINE ; BINDING ; ACID ; STABILIZATION ; INHIBITION
资助项目Drug Innovation Major Project of China[2018ZX09735001-002-005] ; Personalized MedicinesMolecular 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[2019284]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000734977300001
出版者SPANDIDOS PUBL LTD
源URL[http://119.78.100.183/handle/2S10ELR8/300809]  
专题新药研究国家重点实验室
通讯作者Xuan, Lijiang
作者单位1.Chinese Acad Sci, Shanghai Clin Res Ctr, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Fudan Univ, Shanghai Xuhui Cent Hosp, Cent Lab, Zhongshan Xuhui Hosp, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714		 Li, Huihui,Li, Jun,Zhang, Xianjing,et al. Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9[J]. EXPERIMENTAL AND THERAPEUTIC MEDICINE,2021,22(6):9.
APA Li, Huihui.,Li, Jun.,Zhang, Xianjing.,Li, Jiaomeng.,Xi, Cong.,...&Xuan, Lijiang.(2021).Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9.EXPERIMENTAL AND THERAPEUTIC MEDICINE,22(6),9.
MLA Li, Huihui,et al."Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9".EXPERIMENTAL AND THERAPEUTIC MEDICINE 22.6(2021):9.

入库方式： OAI收割

来源：上海药物研究所

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