title: 24(S)-Saringosterol from edible marine seaweed Sargassum fusiforme is a novel selective LXRβ agonist.
abstract: 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.
authors.affiliation: 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.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Jiao
authors.initials: J
authors.lastname: Liu
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Fu
authors.forename: Cheng
authors.initials: C
authors.lastname: Ye
authors.forename: Renshuai
authors.initials: R
authors.lastname: Zhang
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Song
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haihua
authors.initials: H
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.forename: Hongbing
authors.initials: H
authors.lastname: Liu
mesh_terms: D000924:Anticholesteremic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002681:China; D002784:Cholesterol / Q000378:metabolism; D055951:Functional Food / Q000032:analysis*; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D000071518:Liver X Receptors; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010140:Pacific Ocean; D020033:Protein Isoforms / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D044647:Sargassum / Q000737:chemistry*; D012624:Seaweed / Q000737:chemistry*; D013237:Stereoisomerism; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000924:Anticholesteremic Agents; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D020033:Protein Isoforms; D011994:Recombinant Proteins; C442582:saringosterol; D002784:Cholesterol; D013265:Stigmasterol
keywords: 24(S)-saringosterol; Sargassum fusiforme; cholesterol metabolism; phytosterols; selective LXRβ agonist