Antipyretic and anti-inflammatory effects of asiaticoside in lipopolysaccharide-treated rat through up-regulation of heme oxygenase-1

Phytother Res. 2013 Aug;27(8):1136-42. doi: 10.1002/ptr.4838. Epub 2012 Sep 12.

Abstract

Asiaticoside (AS), a triterpenoid isolated from Centella asiatica, has been found to exhibit antioxidant and anti-inflammatory activities in several experimental animal models. However, the underlying mechanisms remain elusive. In this study, we provide experimental evidences that AS dose-dependently inhibited lipopolysaccharide (LPS)-induced fever and inflammatory response, including serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 production, liver myeloperoxidase (MPO) activity, brain cyclooxygenase-2 (COX-2) protein expression and prostaglandin E2 (PGE2 ) production. Interestingly, AS increased serum IL-10 level, liver heme oxygenase-1 (HO-1) protein expression and activity. Furthermore, we found that the suppressive effects of AS on LPS-induced fever and inflammation were reversed by pretreatment with ZnPPIX, a HO-1 activity inhibitor. In summary, our results suggest that AS has the antipyretic and anti-inflammatory effects in LPS-treated rat. These effects could be associated with the inhibition of pro-inflammatory mediators, including TNF-α and IL-6 levels, COX-2 expression and PGE2 production, as well as MPO activity, which might be mediated by the up-regulation of HO-1.

Keywords: asiaticoside; fever; heme oxygenase-1; inflammation; lipopolysaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antipyretics / pharmacology*
  • Centella / chemistry
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Inflammation / drug therapy
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Lipopolysaccharides
  • Liver / enzymology
  • Male
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Triterpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / blood
  • Up-Regulation / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antipyretics
  • Interleukin-6
  • Lipopolysaccharides
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Peroxidase
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Dinoprostone
  • asiaticoside