title: Auraptene suppresses inflammatory responses in activated RAW264 macrophages by inhibiting p38 mitogen-activated protein kinase activation.
abstract: METHODS
  Inflammation plays a key role in obesity-related pathologies such as insulin resistance and type 2 diabetes. Hypertrophied adipocytes trigger the enhancement of macrophage infiltration and the release of various proinflammatory factors in obese adipose tissue. In this study, we examined whether auraptene, a citrus-fruit-derived compound, could suppress the production of inflammatory factors that mediate the interaction between adipocytes and macrophages.
  
  
  RESULTS
  Experiments using a co-culture system of 3T3-L1 adipocytes and RAW264 macrophages showed that auraptene reduced the production of nitric oxide and tumor necrosis factor-α. In RAW264 macrophages, auraptene also suppressed the inflammation induced by either LPS or the conditioned medium derived from 3T3-L1 adipocytes. In addition, auraptene inhibited the phosphorylation of the p38 mitogen-activated protein kinase and suppressed the production of proinflammatory mediators in activated macrophages.
  
  
  CONCLUSIONS
  Our findings indicate that auraptene exhibits anti-inflammatory properties by suppressing the production of inflammatory factors that mediate the interaction between adipocytes and macrophages, suggesting that auraptene is a valuable food-derived compound with a potential to attenuate chronic inflammation in adipose tissue and to improve obesity-related insulin resistance.
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors.forename: Shan
authors.initials: S
authors.lastname: Lin
authors.forename: Shizuka
authors.initials: S
authors.lastname: Hirai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yano
authors.forename: Takao
authors.initials: T
authors.lastname: Sasaki
authors.forename: Rina
authors.initials: R
authors.lastname: Yu
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D002957:Citrus / Q000737:chemistry; D018920:Coculture Techniques; D003374:Coumarins / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D005638:Fruit / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000009:adverse effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003374:Coumarins; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; C105832:aurapten
keywords: Adipose tissue; Auraptene; Inflammation; Insulin resistance; Macrophages