title: Anti-atherosclerotic potential of baicalin mediated by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1/ABCG1 pathway.
abstract: BACKGROUND
  Atherosclerosis (AS) is associated with severe cardiovascular disease. The anti-inflammatory, anti-oxidation, and lipid regulating properties of baicalin suggest potential as an anti-atherosclerotic agent. We therefore investigated whether baicalin can protect against the development of atherosclerosis in an AS rabbit model and explored the underling mechanisms in THP-1 macrophages.
  
  
  RESULTS
  In vivo, treatment with baicalin markedly decreased atherosclerotic lesion sizes and lipid accumulation in AS rabbit carotid arteries. Western blotting revealed that the protein expression levels of both peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor alpha (LXRα) were up-regulated in the baicalin group compared with the model group. In vitro, baicalin restricted oxidized-low density lipoprotein (ox-LDL)-induced intracellular lipid accumulation and foam cell formation in THP-1 macrophages. Molecular data showed that baicalin significantly increased the expression levels of PPARγ, LXRα, ATP binding cassette transporters (ABC) A1 and ABCG1. Cell transfection experiments (including PPARγ and LXRα siRNAs) suggested that the effects of baicalin are mediated by the PPARγ-LXRα signalling pathway, which stimulates the expression of ABCA1 and ABCG1.
  
  
  CONCLUSIONS
  These results suggest that baicalin potentially exerts anti-atherosclerosis effects, possibly through the PPARγ-LXRα-ABCA1/ABCG1 pathway, by promoting efflux of cholesterol from macrophages and delaying the formation of foam cells.
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: doctorxinweihe@163.com.
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: He
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: yd@enzemed.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: liwl@enzemed.com.
authors.forename: Wei-Ling
authors.initials: WL
authors.lastname: Li
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: zhengzhou@enzemed.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: 598298676@qq.com.
authors.forename: Chen-Ling
authors.initials: CL
authors.lastname: Lv
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: licai@enzemed.com.
authors.forename: Cai
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: xs_liup@enzemed.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: xucq@enzemed.com.
authors.forename: Chun-Qiang
authors.initials: CQ
authors.lastname: Xu
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: huxf@enzemed.com.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Hu
authors.affiliation: Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: doctorxinweihe@163.com.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Jin
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D005487:Foam Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008055:Lipids / Q000097:blood; D000071518:Liver X Receptors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011817:Rabbits
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D005419:Flavonoids; D008055:Lipids; D000071518:Liver X Receptors; D047495:PPAR gamma; D034741:RNA, Small Interfering; C038044:baicalin; D002784:Cholesterol
keywords: Atherosclerosis; Baicalin; Cholesterol efflux; LXRα; PPARγ