24(S)-Saringosterol from Edible Marine Seaweed Sargassum fusiforme Is a Novel Selective LXRβ Agonist
24(S)-Saringosterol from Edible Marine Seaweed Sargassum fusiforme Is a Novel Selective LXRβ Agonist
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DOI：
10.1021/jf500083r
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发表时间：
2014-07-02
影响因子：
6.1
通讯作者：
Liu, Hongbing
中科院分区：
文献类型：
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作者：
Chen, Zhen;Liu, Jiao;Liu, Hongbing
膳食植物甾醇已成功地用于降低胆固醇水平，这与一些植物甾醇能够充当肝X受体（LXR）激动剂的事实相关。羊栖菜是一种可食用的海洋海藻，在中药中以其抗动脉粥样硬化的作用而闻名。在该研究中，七种植物甾醇包括岩藻甾醇（1）、沙林甾醇（2）、24-氢过氧-24-乙烯基-胆固醇（3）、29-氢过氧-豆甾-5，24（28）-二烯-3 β-醇（4）、24-亚甲基-胆固醇（5）、24-酮-胆固醇（6）和5 α，8 α-表二氧麦角甾-6，纯化22-二烯-3 β-醇（7），并使用报告基因测定评估其对LXR介导的转录的作用。在这些植物甾醇中，2是刺激LXR α转录活性最有效的化合物，分别为（3.81 +/- 0.15）倍和（14.40 +/- 1.10）倍。2，24（S）-沙林甾醇（2a）和24（R）-沙林甾醇（2b）的两个差向异构体随后通过半制备高效液相色谱法分离。有趣的是，与对照相比，2a在LXR β介导的反式激活中比2b更有效（（3.50 +/- 0.17）倍vs（1.63 +/- 0.12）倍）。一致地，2a在6个细胞系中诱导更高水平的LXR靶基因表达，包括胆固醇逆向转运的关键参与者。这些数据沿着分子建模表明，2a作为选择性LXR β激动剂，是一种有效的天然降胆固醇剂。本研究还证实了S.羊栖菜有助于众所周知的抗动脉粥样硬化功能。
Dietary phytosterols have been successfully used for lowering cholesterol levels, which correlates with the fact that some phytosterols are able to act as liver X receptor (LXR) agonists. Sargassum fusiforme is an edible marine seaweed well-known for its antiatherosclerotic function in traditional Chinese medicine. In this study, seven phytosterols including fucosterol (1), saringosterol (2), 24-hydroperoxy-24-vinyl-cholesterol (3), 29-hydroperoxy-stigmasta-5,24(28)-dien-3 beta-ol (4), 24-methylene-cholesterol (5), 24-keto-cholesterol (6), and 5 alpha,8 alpha-epidioxyergosta-6,22-dien-3 beta-ol (7) were purified and evaluated for their actions on LXR-mediated transcription using a reporter assay. Among these phytosterols, 2 was the most potent compound in stimulating the transcriptional activities of LXR alpha by (3.81 +/- 0.15)-fold and LXR beta by (14.40 +/- 1.10)-fold, respectively. Two epimers of 2, 24(S)-saringosterol (2a) and 24(R)-saringosterol (2b), were subsequently separated by semipreparative high-performance liquid chromatography. Interestingly, 2a was more potent than 2b in LXR beta-mediated transactivation ((3.50 +/- 0.17)-fold vs (1.63 +/- 0.12)-fold) compared with control. Consistently, 2a induced higher expression levels of LXR target genes including key players in reverse cholesterol transport in six cell lines. These data along with molecular modeling suggested that 2a acts as a selective LXR beta agonist and is a potent natural cholesterol-lowering agent. This study also demonstrated that phytosterols in S. fusiforme contributed to the well-known antiatherosderotic function.