title: Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway.
abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α.
authors.affiliation: Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Xu
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Liewen
authors.initials: L
authors.lastname: Pang
authors.forename: Guoqian
authors.initials: G
authors.lastname: Huang
authors.forename: Jiechun
authors.initials: J
authors.lastname: Huang
authors.forename: Meng
authors.initials: M
authors.lastname: Shi
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Sun
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Wang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000096:biosynthesis; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D005663:Furans; D017705:Lignans; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D034741:RNA, Small Interfering; C099252:oxidized low density lipoprotein; D002784:Cholesterol; C071942:arctigenin
keywords: ATP binding cassette transporter A1 (ABCA1); ATP binding cassette transporter G1 (ABCG1); Atherosclerosis; Cholesterol efflux