Esculin exhibited anti-inflammatory activities in vivo and regulated TNF-α and IL-6 production in LPS-stimulated mouse peritoneal macrophages in vitro through MAPK pathway

Int Immunopharmacol. 2015 Dec;29(2):779-786. doi: 10.1016/j.intimp.2015.08.041. Epub 2015 Sep 26.


Esculin, a coumarinic derivative found in Aesculus hippocastanum L. (Horse-chestnut), has been reported to have potent anti-inflammatory properties. The present study is designed to investigate the protective effects of esculin on various inflammation models in vivo and in vitro and to clarify the possible mechanism. Induced-animal models of inflammation and lipopolysaccharide (LPS)-challenged mouse peritoneal macrophages were used to examine the anti-inflammatory activity of esculin. In present study, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, and carrageenan-induced mouse pleurisy were attenuated by esculin. In vitro, the pro-inflammatory cytokine levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in supernatant were reduced by esculin. Meanwhile, we found that esculin significantly inhibited LPS-induced activation of mitogen-activated protein kinase (MAPK) pathway in peritoneal macrophages. These results suggest that esculin has potent anti-inflammatory activities in vivo and in vitro, which may involve the inhibition of the MAPK pathway. Esculin may be a promising preventive agent for inflammatory diseases in human.

Keywords: Esculin; Inflammation; Inflammatory cytokines; Mitogen-activated protein kinases; Peritoneal macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Carrageenan
  • Edema / chemically induced
  • Edema / prevention & control
  • Enzyme Activation / drug effects
  • Esculin / pharmacology*
  • Female
  • Interleukin-6 / biosynthesis*
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects*
  • Male
  • Mice
  • Mitogen-Activated Protein Kinases / drug effects*
  • Pleurisy / chemically induced
  • Pleurisy / prevention & control
  • Rats
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Xylenes


  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Xylenes
  • interleukin-6, mouse
  • Esculin
  • Carrageenan
  • Mitogen-Activated Protein Kinases