0 24

Cited 0 times in

Welsh onion extract inhibits PCSK9 expression contributing to the maintenance of the LDLR level under lipid depletion conditions of HepG2 cells

Authors
 Hyo-Kyoung Choi  ;  Jin-Taek Hwang  ;  Tae-Gyu Nam  ;  Sung Hee Kim  ;  Dong-Kook Min  ;  Sahng Wook Park  ;  Min-Yu Chung 
Citation
 FOOD & FUNCTION, Vol.8(12) : 4582-4591, 2017-12 
Journal Title
 FOOD & FUNCTION 
ISSN
 2042-6496 
Issue Date
2017-12
MeSH
Cholesterol, LDL / metabolism ; Gene Expression / drug effects ; Hep G2 Cells ; Hepatocyte Nuclear Factor 1-alpha / genetics ; Hepatocyte Nuclear Factor 1-alpha / metabolism ; Humans ; Lipid Metabolism / drug effects* ; Onions / chemistry* ; Plant Extracts / chemistry ; Plant Extracts / pharmacology* ; Proprotein Convertase 9 / genetics* ; Proprotein Convertase 9 / metabolism ; Receptors, LDL / genetics* ; Receptors, LDL / metabolism ; Serum / chemistry ; Serum / metabolism ; Sterol Regulatory Element Binding Protein 2 / genetics ; Sterol Regulatory Element Binding Protein 2 / metabolism
Abstract
Statins mediate the transactivation of PCSK9, which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of the present study was to investigate the mechanism of action by which Welsh onion (Allium fistulosum L. [family Amaryllidaceae]) extract (WOE) regulates LDLR and PCSK9. HepG2 cells were cultured under lipid depletion conditions using a medium supplemented with delipidated serum (DLPS). WOE (50, 100, 200, and 400 μg ml-1) significantly attenuated the DLPS-mediated increases in LDLR, PCSK9, and SREBP2 gene expression. While WOE treatment maintained the DLPS-mediated increases in LDLR protein expression, it dose-dependently and significantly attenuated the DLPS-mediated increases in the protein content of PCSK9. The suppression of PCSK9 was associated with the WOE-mediated reductions in SREBP2, but not HNF1α. WOE also dose-dependently reduced PCSK9 protein expression that was otherwise markedly induced by concomitant statin treatment. WOE-mediated PCSK9 inhibition contributed to LDLR lysosomal degradation suppression, and subsequent LDLR protein stabilization. HPLC analysis indicated that WOE contains kaempferol, quercetin, ferulic acid, and p-coumaric acid. Kaempferol and p-coumaric acid contributed to the maintenance of LDLR expression by inhibiting PCSK9 in lipid depleted HepG2 cells. Altogether, these findings suggest that WOE inhibits PCSK9 transcription and protein expression via the reduction of SREBP2, and decreased PCSK9 further contributes to LDLR degradation prevention and LDLR protein stabilization under conditions of lipoprotein deficiency. The PCSK9 inhibition-mediated mechanism of WOE was likely attributed to the action of kaempferol and p-coumaric acid present in WOE.
Full Text
https://pubs.rsc.org/en/content/articlelanding/2017/FO/C7FO00562H#!divAbstract
DOI
10.1039/c7fo00562h
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Min, Dong Kook(민동국)
Park, Sahng Wook(박상욱) ORCID logo https://orcid.org/0000-0002-9594-7074
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/178323
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links