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| 標題: | Xanthohumol Suppresses NPC1L1 Gene Expression through Downregulation of HNF-4 alpha( )and Inhibits Cholesterol Uptake in Caco-2 Cells |
| 作者: | Thang, Sang Kim
Chen, Pei-Yi
Gao, Wan-Yun
Wu, Ming-Jiuan
Pan, Min-Hsiung
Yen, Jui-Hung |
| 貢獻者: | Tzu Chi Univ, Inst Med Sci
Hualien Tzu Chi Hosp, Buddhist Tzu Chi Fdn, Ctr Med Genet
Tzu Chi Univ, Dept Mol Biol & Human Genet
Chia Nan Univ Pharm & Sci, Dept Biotechnol
Natl Taiwan Univ, Inst Food Sci & Technol |
| 關鍵字: | xanthohumol
cholesterol absorption
NPC1L1
HNF-4 alpha
statin |
| 日期: | 2019 |
| 上傳時間: | 2020-07-29 13:54:32 (UTC+8) |
| 出版者: | AMER CHEMICAL SOC |
| 摘要: | Xanthohumol (Xan) is a prenylated chalcone mainly found in hops; it has been demonstrated to function against hypercholesterolemia, hyperlipidemia, and atherosclerosis. In this study, we focused on the hypocholesterolemic effect of Xan on cholesterol uptake and the underlying molecular mechanisms of Xan in human intestinal Caco-2 cells. The microarray data showed that Niemann-Pick C1-like 1 (NPC1L1), an essential transporter for dietary cholesterol absorption, was significantly downregulated in Xan-treated Caco-2 cells. We demonstrated that Xan (10 and 20 mu M) suppressed the mRNA and protein expression of NPC1L1 by 0.65 +/- 0.12-fold and 0.54 +/- 0.15-fold and 0.72 +/- 0.04-fold and 0.44 +/- 0.12-fold, respectively, compared to that of the vehicle-treated Caco-2 cells. Moreover, Xan (10 and 20 mu M) significantly inhibited cholesterol uptake by approximately 12 and 32% in Caco-2 cells. NPC1L1 promoter activity was significantly suppressed by Xan, and a DNA element within the NPC1L1 promoter involved in Xan-mediated NPC1L1 reduction located between the -120 and -20 positions was identified. Moreover, Xan markedly decreased the mRNA and protein levels of hepatocyte nuclear factor 4 alpha (HNF-4 alpha), a critical activator of NPC1L1 transcription, and subsequently attenuated HNF-4 alpha/NPC1L1 promoter complex formation, resulting in the suppression of NPC1L1 gene expression. Finally, we demonstrated that Xan markedly abolished lovastatin-induced NPC1L1 overexpression in Caco-2 cells. These findings reveal that Xan suppresses NPC1L1 expression via downregulation of HNF-4 alpha and exerts inhibitory effects on cholesterol uptake in the intestinal Caco-2 cells. Our findings suggest Xan could serve as a potential cholesterol-lowering agent and supplement for statin therapy. |
| 關聯: | Journal of Agricultural and Food Chemistry, v.67, n.40, pp. |
| 顯示於類別: | [生物科技系(所)] 期刊論文
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