Auraptene suppresses inflammatory responses in activated RAW264 macrophages by inhibiting p38 mitogen-activated protein kinase activation

Mol Nutr Food Res. 2013 Jul;57(7):1135-44. doi: 10.1002/mnfr.201200611. Epub 2013 Mar 14.


Scope: 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.

Methods and 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.

Conclusion: 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.

Keywords: Adipose tissue; Auraptene; Inflammation; Insulin resistance; Macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line, Tumor
  • Chemokine CCL2 / metabolism
  • Citrus / chemistry
  • Coculture Techniques
  • Coumarins / pharmacology*
  • Culture Media, Conditioned
  • Fruit / chemistry
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Insulin Resistance
  • Lipopolysaccharides / adverse effects
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism
  • Obesity / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / genetics*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Anti-Inflammatory Agents
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Coumarins
  • Culture Media, Conditioned
  • Lipopolysaccharides
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • p38 Mitogen-Activated Protein Kinases
  • aurapten