A novel small molecule liver X receptor transcriptional regulator, nagilactone B, suppresses atherosclerosis in apoE-deficient mice
文献类型：期刊论文
| 作者 | Gui, Yuzhou1; Yao, Sheng1 ; Yan, Hong1; Hu, Liang1; Yu, Chengyin2; Gao, Fei1; Xi, Cong1; Li, Huihui1; Ye, Yang1; Wang, Yiping1
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| 刊名 | CARDIOVASCULAR RESEARCH
 |
| 出版日期 | 2016-10-01 |
| 卷号 | 112期号:1页码:502-514 |
| 关键词 | Atherosclerosis Macrophage ATP-binding cassette transporter A1 ATP-binding cassette transporter G1 Liver X receptor |
| ISSN号 | 0008-6363 |
| DOI | 10.1093/cvr/cvw183 |
| 文献子类 | Article |
| 英文摘要 | Atherosclerosis is the most common cause of cardiovascular diseases, such as myocardial infarction and stroke. We hypothesized that nagilactone B (NLB), a small molecule extracted from the root bark of Podocarpus nagi (Podocarpaceae), suppresses atherosclerosis in an atherosclerotic mouse model. Male apoE-deficient mice on C57BL/6J background received NLB (10 and 30 mg/kg) for 12 weeks. Compared with the model group, NLB treatment (10 and 30 mg/kg) significantly reduced en face lesions of total aorta areas. In RAW264.7 cells, NLB significantly ameliorated cholesterol accumulation in macrophages via enhancing apolipoprotein A-I and HDL-mediated cholesterol efflux. Mechanistically, NLB induced messenger RNA and protein expression of the ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 and THP-1 cells. Liver X receptor (LXR) site mutations in the mouse ABCA1 promoter abrogated NLB-mediated luciferase reporter activity. LXR alpha and LXR beta small interfering RNA suppressed NLB-mediated induction of ABCA1 expression. Consistent with in vitro results, NLB induced ABCA1 expression and suppressed macrophage areas in the aortic sinus. Moreover, NLB treatment did not induce the protein expression of LXR in liver. Hepatic and intestinal cholesterol accumulation was significantly alleviated on NLB treatment. Besides, NLB significantly improved plasma lipid profiles in apoE-deficient mice. Selective LXR activation in macrophages with NLB induces ABCA1- and ABCG1-mediated cholesterol efflux while exerting minimal effects on lipogenesis and lipid accumulation in liver, resulting in regression of atherosclerosis, and therefore might be a promising strategy for therapeutics. |
| WOS关键词 | ATP-BINDING CASSETTE ; REVERSE CHOLESTEROL TRANSPORT ; LXR-ALPHA ; PLASMA-CHOLESTEROL ; CELL-LINES ; ABCA1 GENE ; EFFLUX ; LIPOPROTEIN ; MACROPHAGES ; METABOLISM |
| 资助项目 | National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' from the National Health and Family Planning Commission of the People's Republic of China[2015ZX09103002] |
| WOS研究方向 | Cardiovascular System & Cardiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000387579900009 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275874]  |
| 专题 | 天然药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Ye, Yang; Wang, Yiping |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 2.Univ Portsmouth, Sch Pharm & Biomed Sci, White Swan Rd, Portsmouth PO1 2DT, Hants, England |
| 推荐引用方式 GB/T 7714 | Gui, Yuzhou,Yao, Sheng,Yan, Hong,et al. A novel small molecule liver X receptor transcriptional regulator, nagilactone B, suppresses atherosclerosis in apoE-deficient mice[J]. CARDIOVASCULAR RESEARCH,2016,112(1):502-514. |
| APA | Gui, Yuzhou.,Yao, Sheng.,Yan, Hong.,Hu, Liang.,Yu, Chengyin.,...&Wang, Yiping.(2016).A novel small molecule liver X receptor transcriptional regulator, nagilactone B, suppresses atherosclerosis in apoE-deficient mice.CARDIOVASCULAR RESEARCH,112(1),502-514. |
| MLA | Gui, Yuzhou,et al."A novel small molecule liver X receptor transcriptional regulator, nagilactone B, suppresses atherosclerosis in apoE-deficient mice".CARDIOVASCULAR RESEARCH 112.1(2016):502-514. |
入库方式： OAI收割
来源：上海药物研究所
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