Xanthohumol Suppresses Mylip/Idol Gene Expression and Modulates LDLR Abundance and Activity in HepG2 Cells

doi:10.1021/acs.jafc.7b02282

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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
显示于类别:	[生物科技系(所)] 期刊論文

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