Hesperetin Upregulates ABCA1 Expression and Promotes Cholesterol Efflux from THP-1 Macrophages

详细信息    查看全文

• 作者：Akio Iio ; Kenji Ohguchi ; Munekazu Iinuma ; Yoshinori Nozawa ; Masafumi Ito
• 刊名：Journal of Natural Products
• 出版年：2012
• 出版时间：April 27, 2012
• 年：2012
• 卷：75
• 期：4
• 页码：563-566
• 全文大小：202K
• 年卷期：v.75,no.4(April 27, 2012)
• ISSN：1520-6025

文摘

ABCA1, a member of the ATP-binding cassette transporter family, regulates high-density lipoprotein (HDL) metabolism and cholesterol transport. Its expression is upregulated mainly by the activation of the liver X receptor (LXR). Since ABCA1 plays a pivotal role in cholesterol and HDL metabolism, identification of a compound capable of increasing its expression may be beneficial for the prevention and therapy of atherosclerosis. Firefly luciferase reporter assays were developed for human ABCA1 promoters and LXR enhancers, and an in-house phytochemical library was screened. It was found that a citrus flavonoid, hesperetin (1), increased ABCA1 promoter and LXR enhancer activities in THP-1 macrophages. It was also found that this flavonoid promoted PPAR-enhancing activity. In accordance with these findings, 1 increased mRNA and protein expression of ABCA1 and consequently upregulated ApoA-I-mediated cholesterol efflux. These results provide evidence that 1 promotes ApoA-I-mediated cholesterol efflux from macrophages by increasing ABCA1 expression through the activation of LXR伪 and PPAR纬.