Role of hesperetin in LDL-receptor expression in hepatoma HepG2 cells

BMC Complementary and Alternative Medicine

Research Article

Wesam H. Abdulaal¹  Mazin A. Zamzami¹  Hani Choudhry²  Said S. Moselhy³  Bruce Middleton⁴  Nora A. Bawazeer⁵ 

[1] Department of Biochemistry, Cancer and mutagensis Unit, King Fahad Medical Research Center, KingAbdulaziz University, Jeddah, Saudi Arabia;Department of Biochemistry, Faculty of Science, Cancer and mutagensis unit, Center of Innovation in Personalized Medicine, King Fahd Center for medical Research, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Biochemistry, Faculty of Science, Ain shams University, Cairo, Egypt;Department of Biochemistry, Medical School, Nottingham University, Nottingham, UK;Department of Home Economics, Taif University, Taif, Saudi Arabia;

关键词: LDL-receptor;    Hesperetin;    HepG2 cell line;   

DOI  :  10.1186/s12906-016-1165-2

 received in 2015-09-26, accepted in 2016-06-15,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHigh plasma concentration of low-density lipoprotein cholesterol (LDL-c) plays a significant role in the incidence of atherosclerosis and coronary heart diseases. The aim of this study was to investigate the mechanism by which the citrus flavonoid, hesperetin, regulates the LDL receptor (LDLr) gene in the human liver using the human hepatoma cell line, HepG2.MethodsLuciferase reporter gene assays were performed (in the absence of lipoprotein) to measure the activity of the LDLr promoter and the promoters of the sterol regulatory element binding protein (SREBP) transcription factors that control the LDLr promoter.ResultsOnly SREBP-1 promoter activity was significantly increased 4 h after exposure to 200 μM hesperetin. However, after 24 h incubation with 200 μM hesperetin, the activities of all the promoter-constructs, SREBP-1a, -1c, -2 and LDLr, were significantly increased. The effects of 200 μM hesperetin on elevating LDLr mRNA levels were possibly due to regulation of LDLr gene transcription by SREBP-la and SREBP-2.ConclusionsWe conclude that 200 μM hesperetin was likely to have stimulated LDLr gene expression in human hepatoma HepG2 cells via increased phosphorylation of PI3K andERK1/2, which increased SREBP-1a and SREBP-2 mRNA levels and enhanced the maturation of the encoded proteins. This may lead to lower plasma LDL cholesterol; therefore, diets supplemented with hesperidin might provide cardio-protective effects and reduce mortality and morbidity from coronary heart diseases.

【 授权许可】

CC BY   
© The Author(s). 2016