title: The anti-atherogenic properties of sesamin are mediated via improved macrophage cholesterol efflux through PPARγ1-LXRα and MAPK signaling.
abstract: BACKGROUND
  Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood.
  
  
  OBJECTIVE
  This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux.
  
  
  METHODS
  PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays.
  
  
  RESULTS
  The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p<0.001, p<0.001, p<0.001, respectively) and LXRα (p=0.002, p<0.001, p<0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p<0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p<0.001) and 4.2-fold (p<0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p<0.001), 4.2-fold (p<0.001), and 4.2-fold (p<0.001), respectively, via MAPK signaling.
  
  
  CONCLUSIONS
  Our findings shed light on the molecular mechanism(s) underlying sesamins anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.
authors.affiliation: Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, Sharjah, United Arab Emirates.
authors.forename: Amin F
authors.initials: AF
authors.lastname: Majdalawieh
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Ro
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D016466:CHO Cells; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004149:Dioxoles / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D000071518:Liver X Receptors; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D004149:Dioxoles; D017705:Lignans; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D002784:Cholesterol; D020928:Mitogen-Activated Protein Kinases; C054125:sesamin
keywords: LXRα; MAPK; PPARγ1; cholesterol efflux; macrophages; sesamin