잠시만 기다려 주세요. 로딩중입니다.

Butein Synergizes with Statin to Upregulate Low-Density Lipoprotein Receptor Through HNF1α-Mediated PCSK9 Inhibition in HepG2 Cells

Journal of Medicinal Food 2020년 23권 10호 p.1102 ~ 1108
황진택, 김효진, 최호경, 박재호, 정상원, 정민유,
소속 상세정보
황진택 ( Hwang Jin-Taek ) - Korea Food Research Institute
김효진 ( Kim Hyo-Jin ) - Korea Food Research Institute
최호경 ( Choi Hyo-Kyoung ) - Korea Food Research Institute
박재호 ( Park Jae-Ho ) - Korea Food Research Institute
정상원 ( Chung Sang-Won ) - Korea Food Research Institute
정민유 ( Chung Min-Yu ) - Korea Food Research Institute

Abstract


Downregulation of the low-density lipoprotein (LDL) receptor (LDLR) can lead to hypercholesterolemia and related conditions, including cardiovascular diseases. Statins are a class of LDL cholesterol-lowering agents and are best-selling medications for patients at high risk of developing cardiovascular diseases. Indeed, statins upregulate LDLR and proprotein convertase subtilisin/kexin type 9a (PCSK9), leading to LDLR lysosomal degradation, which interferes with the attenuation of hypercholesterolemia. In the present study, butein was found to decrease extracellular PCSK9 levels by reducing its mRNA expression, which was attributable to butein-mediated downregulation of HNF1α in HepG2 cells. Butein-mediated PCSK9 inhibition further reversed LDLR protein synthesis inhibition, which possibly occurred through butein-mediated inhibition of LDLR degradation. When treated as a combination of butein and a statin, butein reduced statin-mediated enhancement of PCSK9 protein expression. This resulted in a synergistic enhancement of LDLR protein expression, whereas butein alone marginally increased LDLR protein expression. These findings suggest that butein, a novel PCSK9 inhibitor, may be a potential alternative or adjunct to statin treatment.

키워드

butein; HepG2 cells; LDLR; PCSK9; statins

원문 및 링크아웃 정보

등재저널 정보