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    標題: Xanthohumol Suppresses Mylip/Idol Gene Expression and Modulates LDLR Abundance and Activity in HepG2 Cells
    作者: Chen, Shih-Fen
    Chen, Pei-Yi
    Hsu, Hao-Jen
    Wu, Ming-Jiuan
    Yen, Jui-Hung
    貢獻者: Tzu Chi Univ, Dept Mol Biol & Human Genet
    BuddhistTzu Chi Gen Hosp, Ctr Med Genet
    Tzu Chi Univ, Dept Life Sci
    Chia Nan Univ Pharm & Sci, Dept Biotechnol
    關鍵字: xanthohumol
    LDLR
    Mylip/Idol
    LXR alpha
    simvastatin
    日期: 2017-09-13
    上傳時間: 2018-11-30 15:52:36 (UTC+8)
    出版者: Amer Chemical Soc
    摘要: Xanthohumol, a prenylated flavonoid found in hops (Humulus lupulus L.), exhibits multiple biological activities such as antiatherosderosis and hypolipidemic activities. In this study, we aim to investigate the hypocholesterolemic effects and molecular mechanisms of xanthohumol in hepatic cells. We found that xanthohumol (10 and 20 mu M) increased the amount of cell-surface low-density lipoprotein receptor (LDLR) from 100.0 +/- 2.1% to 115.0 +/- 1.3% and 135.2 +/- 2.7%, and enhanced the LDL uptake activity from 100.0 +/- 0.9% to 139.1 +/- 13.2% in HepG2 cells (p < 0.01). The mRNA levels of LDLR, HMGCR, and PCSK9 were not altered. Xanthohumol (20 mu M) reduced the expression of inducible degrader of the LDL receptor (Mylip/Idol) mRNA and protein by approximately 45% ( p< 0.01), which was reported to be associated with increases of LDLR level. We demonstrated that xanthohumol suppressed hepatic Mylip/Idol expression via counteracting liver X receptor (LXR) activation. The molecular docking results predicted that xanthohumol has a high binding affinity to interact with the LXR alpha ligand-binding domain, which may result in attenuation of LXR alpha-induced Mylip/Idol expression. Finally, we demonstrated that the Mylip/Idol expression and LDLR activity were synergistically changed by a combination of xanthohumol and simvastatin treatment. Our findings indicated that xanthohumol may regulate the LXR Mylip/Idol axis to modulate hepatic LDLR abundance and activity.
    關聯: Journal of Agricultural and Food Chemistry, v.65, n.36, pp.7908-7918
    Appears in Collections:[生物科技系(所)] 期刊論文

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