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	Betulin attenuates atherosclerosis in apoe(-/-) mice by up-regulating abca1 and abcg1
	Gui, Yu-zhou1,2; Yan, Hong1,2; Gao, Fei1,2; Xi, Cong1,2; Li, Hui-hui1,2; Wang, Yi-ping1,2
刊名	Acta pharmacologica sinica
	2016-10-01
卷号	37期号:10页码:1337-1348
关键词	Atherosclerosis Macrophage Betulin Atorvastatin T0901317 25-oh cholesterol Atp-binding cassette transporter a1 Atp-binding cassette transporter g1 Sterol-responsive element-binding protein
ISSN号	1671-4083
DOI	10.1038/aps.2016.46
通讯作者	Wang, yi-ping(ypwang@mail.shcnc.ac.cn)
英文摘要	Aim: betulin is a pentacyclic triterpenoid isolated from the bark of yellow and white birch trees with anti-cancer and anti-malaria activities. in this study we examined the effects of betulin on atherosclerosis in apoe(-/-) mice and the underlying mechanisms. methods: murine macrophage raw264.7 cells and human monocyte-derived thp-1 cells were tested. foam cell formation was detected with oil red o staining. cholesterol efflux was assessed using [h-3]-cholesterol efflux assay. the expression of atp-binding cassette transporter a1 and g1 (abca1 and abcg1) was examined using rt-pcr and western-blotting. the abca1 promoter activity was evaluated using luciferase activity assay. male apoe(-/-) mice fed on a high-fat-diet (hfd), and received betulin (20 and 40 mg.kg(-1).d(-1), ig) for 12 weeks. the macrophage content and abca1 expression in the aortic sinuses were evaluated with immunofluorescence staining. the hepatic, intestinal and fecal cholesterol were also analyzed in the mice. results: in raw264.7 cells, betulin (0.1-2.5 mu g/ml) dose-dependently ameliorated oxldl-induced cholesterol accumulation and enhanced cholesterol efflux. in both raw264.7 and thp-1 cells, betulin increased the expression of abca1 and abcg1 via suppressing the transcriptional repressors sterol-responsive element-binding proteins (srebps) that bound to e-box motifs in abca1 promoter, whereas e-box binding site mutation markedly attenuated betulin-induced abca1 promoter activity. in hfd-fed apoe(-/-) mice, betulin administration significantly reduced lesions in en face aortas and aortic sinuses. furthermore, betulin administration significantly increased abca1 expression and suppressed macrophage positive areas in the aortic sinuses. moreover, betulin administration improved plasma lipid profiles and enhanced fecal cholesterol excretion in the mice. conclusion: betulin attenuates atherosclerosis in apoe(-/-) mice by promoting cholesterol efflux in macrophages.
WOS关键词	ATP-BINDING CASSETTE ; REVERSE CHOLESTEROL TRANSPORT ; FOAM CELL ACCUMULATION ; APOLIPOPROTEIN-E ; DEFICIENT MICE ; KNOCKOUT MICE ; X RECEPTOR ; EFFLUX ; PROTEIN ; MACROPHAGES
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
WOS类目	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000385634300007
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2374805
专题	中国科学院大学
通讯作者	Wang, Yi-ping
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Gui, Yu-zhou,Yan, Hong,Gao, Fei,et al. Betulin attenuates atherosclerosis in apoe(-/-) mice by up-regulating abca1 and abcg1[J]. Acta pharmacologica sinica,2016,37(10):1337-1348.
APA	Gui, Yu-zhou,Yan, Hong,Gao, Fei,Xi, Cong,Li, Hui-hui,&Wang, Yi-ping.(2016).Betulin attenuates atherosclerosis in apoe(-/-) mice by up-regulating abca1 and abcg1.Acta pharmacologica sinica,37(10),1337-1348.
MLA	Gui, Yu-zhou,et al."Betulin attenuates atherosclerosis in apoe(-/-) mice by up-regulating abca1 and abcg1".Acta pharmacologica sinica 37.10(2016):1337-1348.

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