Identification of a Naturally Occurring Rexinoid, Honokiol, That Activates the Retinoid X Receptor
Identification of a Naturally Occurring Rexinoid, Honokiol, That Activates the Retinoid X Receptor
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DOI：
10.1021/np100120c
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发表时间：
2010-08-01
影响因子：
5.1
通讯作者：
Inoue, Makoto
中科院分区：
文献类型：
--
作者：
Kotani, Hitoshi;Tanabe, Hiroki;Inoue, Makoto
筛选了86种天然药物中的类维生素A X受体（RXR）配体，结果表明厚朴树皮的甲醇提取物在荧光素酶报告基因检测中显著激活RXR α的转录活性。此后，和诺酮（1）被分离为能够作为天然rexinoid选择性激活RXR的成分，但不是RAR α。1的活性比植烷酸和二十二碳六烯酸的活性更有效，植烷酸和二十二碳六烯酸都是已知的天然RXR激动剂。和诺平（1）能够激活RXR/LXR异源二聚体，导致RAW 264.7细胞中ATP结合盒转运蛋白At mRNA和蛋白质表达的诱导，以及腹腔巨噬细胞[H-3]胆固醇流出的增加。1的这些作用在LXR激动剂22（R）-羟基胆固醇的存在下协同增强。获得的结果表明，1，一个新发现的天然rexinoid，调节RXR/LXR异源二聚体的功能，并通过激活RXR/LXR异源二聚体诱导ABCA 1来消除泡沫细胞的形成。
Screening of a total of 86 crude drugs for retinoid X receptor (RXR) ligands demonstrated that the methanol extract of the bark of Magnolia obovata markedly activated the transcriptional activity of RXR alpha in luciferase reporter assays. Thereafter, honokiol (1) was isolated as a constituent able to activate RXR selectively as a natural rexinoid, but not RAR alpha. The activity of 1 was more potent than those of phytanic acid and docosahexaenoic acid, both of which are known to be natural RXR agonists. Honokiol (1) is capable of activating a RXR/LXR heterodimer, resulting in the induction of ATP-binding cassette transporter At mRNA and protein expression in RAW264.7 cells, as well as an increase in [H-3]cholesterol efflux from peritoneal macrophages. These effects of 1 were enhanced synergistically in the presence of an LXR agonist, 22(R)-hydroxycholesterol. The results obtained demonstrate that 1, a newly identified natural rexinoid, regulates the functions of RXR/LXR heterodimer and abrogates foam cell formation by the induction of ABCA1 via activation of the RXR/LXR heterodimer.