title: Osthole inhibits inflammatory cytokine release through PPARα/γ-mediated mechanisms in LPS-stimulated 3T3-L1 adipocytes.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor (PPAR) α/γ may control inflammatory response by regulating the nuclear factor-kappa B (NF-κB). Osthole may be a dual agonist of PPARα/γ, but whether or not osthole may inhibit inflammatory cytokines in cultured 3T3-L1 adipocytes is unclear.
  
  
  OBJECTIVE
  We investigated the action of osthole and its potential mechanisms in lipopolysaccharide (LPS)-stimulated 3T3-L1 adipocytes.
  
  
  METHODS
  The 3T3-L1 adipocytes stimulated with LPS were cultured and treated with different concentrations of osthole. The inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cultured supernatants were detected by the enzyme-linked immunosorbent assay (ELISA) method, and the protein expressions of PPARα/γ and NF-κB p65 in adipocytes were detected by the Western blot method, respectively.
  
  
  RESULTS
  Following treatment of adipocytes with osthole 0.1-1.6 μM, the TNF-α and IL-6 levels in cultured supernatants were decreased, and the NF-κB p65 protein expression in adipocytes was also decreased, while the PPARα/γ protein expressions were increased. After pretreatment of adipocytes with specific inhibitor(s) of PPARα and /or PPARγ, the inhibitory effects of osthole on TNF-α and IL-6 were decreased or almost cancelled, and the effects on NF-κB p65 protein expression also exhibited similar variations.
  
  
  CONCLUSIONS
  Osthole could inhibit the TNF-α and IL-6 production in LPS-stimulated adipocytes, and its mechanism might be related to reduction of NF-κB expression via activation of PPARα/γ.
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu Province , China and.
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Shang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mei-lin
authors.initials: ML
authors.lastname: Xie
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000276:immunology*; D029969:Angelica; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003374:Coumarins / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D047493:PPAR alpha / Q000276:immunology / Q000378:metabolism*; D047495:PPAR gamma / Q000276:immunology / Q000378:metabolism*
chemical_list: D003374:Coumarins; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D047493:PPAR alpha; D047495:PPAR gamma; C046627:osthol
keywords: 3T3-L1 adipocytes; IL-6; PPARα/γ; TNF-α; osthole