Chen Zhen, Liu Jiao, Fu Zhifei, Ye Cheng, Zhang Renshuai, Song Yiyun, Zhang Ying, Li Haihua, Ying Hao, Liu Hongbing
Key Laboratory of Marine Drugs, Chinese Ministry of Education, Institute of Marine Food and Drugs, School of Medicine and Pharmacy, Ocean University of China , Qingdao 266003, China.
J Agric Food Chem. 2014 Jul 2;62(26):6130-7. doi: 10.1021/jf500083r. Epub 2014 Jun 20.
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-3β-ol (4), 24-methylene-cholesterol (5), 24-keto-cholesterol (6), and 5α,8α-epidioxyergosta-6,22-dien-3β-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 LXRα by (3.81±0.15)-fold and LXRβ 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 LXRβ-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 LXRβ agonist and is a potent natural cholesterol-lowering agent. This study also demonstrated that phytosterols in S. fusiforme contributed to the well-known antiatherosclerotic function.
膳食植物甾醇已成功用于降低胆固醇水平，这与一些植物甾醇能够作为肝脏X受体（LXR）激动剂这一事实相关。羊栖菜是一种可食用的海洋海藻，在传统中医中以其抗动脉粥样硬化功能而闻名。在本研究中，七种植物甾醇，包括岩藻甾醇（1）、锯齿甾醇（2）、24-氢过氧-24-乙烯基胆固醇（3）、29-氢过氧-豆甾-5,24(28)-二烯-3β-醇（4）、24-亚甲基胆固醇（5）、24-酮胆固醇（6）和5α,8α-环氧麦角甾-6,22-二烯-3β-醇（7）被纯化，并使用报告基因测定法评估它们对LXR介导的转录的作用。在这些植物甾醇中，化合物2是刺激LXRα转录活性最有效的化合物，分别为（3.81±0.15）倍，刺激LXRβ转录活性为（14.40±1.10）倍。随后通过半制备高效液相色谱法分离了化合物2的两个差向异构体，24(S)-锯齿甾醇（2a）和24(R)-锯齿甾醇（2b）。有趣的是，与对照相比，在LXRβ介导的反式激活中，2a比2b更有效（（3.50±0.17）倍对（1.63±0.12）倍）。一致地，2a在六种细胞系中诱导了包括逆向胆固醇转运关键参与者在内的LXR靶基因的更高表达水平。这些数据以及分子模拟表明，2a作为一种选择性LXRβ激动剂，是一种有效的天然降胆固醇剂。本研究还表明，羊栖菜中的植物甾醇有助于其众所周知的抗动脉粥样硬化功能。
