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Isofraxidin exhibited anti-inflammatory effects in vivo and inhibited TNF-α production in LPS-induced mouse peritoneal macrophages in vitro via the MAPK pathway.

Abstract
Isofraxidin (IF) is a Coumarin compound that can be isolated from medicinal plants, such as Sarcandra glabra (Thunb.). Nakai is widely used in Asian countries for the treatment of anti-bacterial, anti-inflammatory and anti-tumour action. The present investigation was designed to evaluate the effect of IF on inflammation and nociception. In addition, we investigated a potential novel mechanism to explain the anti-inflammatory properties of IF. In vivo, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, LPS-induced mouse endotoxic shock, acetic acid-induced mice writhing and formalin-induced mouse pain models were used to evaluate the anti-inflammatory activity of IF. In vitro, we examined the effects of IF inhibition on TNF-α production and the regulation of ERK1/2 and p38 phosphorylation activity in LPS-induced mouse peritoneal macrophages. Our results demonstrated that IF can significantly decrease xylene-induced ear edema, carrageenan-induced paw edema, acetic acid-induced writhing and formalin-induced pain. Moreover, IF greatly inhibited the production of TNF-α in the serum of LPS-stimulated mice and peritoneal macrophages, and it decreased phospho-p38 and ERK1/2 protein expression in LPS-stimulated mouse peritoneal macrophages. Overall, our data suggest that IF possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-α and the phosphorylation of p38 and ERK1/2.
AuthorsXiaofeng Niu, Wei Xing, Weifeng Li, Ting Fan, Hua Hu, Yongmei Li
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 14 Issue 2 Pg. 164-71 (Oct 2012) ISSN: 1878-1705 [Electronic] Netherlands
PMID22800929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Coumarins
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Xylenes
  • Formaldehyde
  • isofraxidin
  • Carrageenan
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
  • Carrageenan (administration & dosage)
  • Cells, Cultured
  • Coumarins (administration & dosage)
  • Edema (chemically induced, drug therapy, immunology)
  • Formaldehyde (administration & dosage)
  • Lipopolysaccharides (immunology)
  • MAP Kinase Signaling System (drug effects)
  • Macrophages, Peritoneal (drug effects, immunology)
  • Mice
  • Mice, Inbred Strains
  • Pain (chemically induced, drug therapy, immunology)
  • Phosphorylation (drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Septic (chemically induced, drug therapy, immunology)
  • Tumor Necrosis Factor-alpha (metabolism)
  • Xylenes (administration & dosage)
  • p38 Mitogen-Activated Protein Kinases (metabolism)

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