title: Salvianolic acid B accelerated ABCA1-dependent cholesterol efflux by targeting PPAR-γ and LXRα.
abstract: OBJECTIVE
  Cholesterol efflux has been thought to be the main and basic mechanism by which free cholesterol is transferred from extra hepatic cells to the liver or intestine for excretion. Salvianolic acid B (Sal B) has been widely used for the prevention and treatment of atherosclerotic diseases. Here, we sought to investigate the effects of Sal B on the cholesterol efflux in THP-1 macrophages.
  
  
  METHODS
  After PMA-stimulated THP-1 cells were exposed to 50 mg/L of oxLDL and [(3)H] cholesterol (1.0 μCi/mL) for another 24 h, the effect of Sal B on cholesterol efflux was evaluated in the presence of apoA-1, HDL2 or HDL3. The expression of ATP binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and liver X receptor-alpha (LXRα) was detected both at protein and mRNA levels in THP-1 cells after the stimulation of Sal B. Meanwhile, specific inhibition of PPAR-γ and LXRα were performed to investigate the mechanism.
  
  
  RESULTS
  The results showed that Sal B significantly accelerated apoA-I- and HDL-mediated cholesterol efflux in both dose- and time-dependent manners. Meanwhile, Sal B treatment also enhanced the expression of ABCA1 at both mRNA and protein levels. Then the data demonstrated that Sal B increased the expression of PPAR-γ and LXRα. And the application of specific agonists and inhibitors of further confirmed that Sal exert the function through PPAR-γ and LXRα.
  
  
  CONCLUSIONS
  These results demonstrate that Sal B promotes cholesterol efflux in THP-1 macrophages through ABCA1/PPAR-γ/LXRα pathway.
authors.affiliation: Department of Endocrinology, Shandong Province Hospital Affiliated to Shandong University, 324# Jing 5 Road, Jinan 255021, PR China; Department of Endocrinology, The First Hospital of Zibo, 4# E Mei Shan Dong Road, Zibo 255200, PR China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Yue
authors.affiliation: Department of Cardiology, Central Hospital of Zibo, 54# Gong Qing Tuan Xi Road, Zibo, Shandong Province, PR China. Electronic address: libosubmit@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Endocrinology, The First Hospital of Zibo, 4# E Mei Shan Dong Road, Zibo 255200, PR China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Jing
authors.affiliation: Department of Endocrinology, Shandong Province Hospital Affiliated to Shandong University, 324# Jing 5 Road, Jinan 255021, PR China. Electronic address: guanqingbosubmit@163.com.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Guan
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D053439:Lipoproteins, HDL2 / Q000378:metabolism; D053440:Lipoproteins, HDL3 / 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*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D053630:Depsides
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D001572:Benzofurans; D002784:Cholesterol; D004365:Drugs, Chinese Herbal; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; C577836:ABCA1 protein, human; C000605213:NR1H3 protein, human; C076944:salvianolic acid B; D053630:Depsides
keywords: ABCA1; Cholesterol efflux; LXRα; PPAR-γ; Salvianolic acid B