Asperlin from the marine-derived fungus Aspergillus sp. SF-5044 exerts anti-inflammatory effects through heme oxygenase-1 expression in murine macrophages

J Pharmacol Sci. 2011;116(3):283-95. doi: 10.1254/jphs.10219fp. Epub 2011 Jun 25.

Abstract

Asperlin is a fungal metabolite isolated from Aspergillus sp. SF-5044. In the present study, we isolated asperlin from the marine-derived fungus Aspergillus sp. SF-5044 and demonstrated that it inhibited inducible nitric oxide synthase (iNOS) expression, reduced iNOS-derived NO, suppressed cyclooxygenase (COX)-2 expression, and reduced COX-derived prostaglandin (PG) E₂ production in lipopolysaccharide (LPS)-stimulated RAW264.7 and murine peritoneal macrophages. Similarly, asperlin reduced the production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. In addition, asperlin inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of p65 caused by the stimulation of LPS in RAW264.7 macrophages. Furthermore, asperlin induced heme oxygenase (HO)-1 expression through nuclear translocation of nuclear factor E2-related factor 2 and increased HO activity in RAW264.7 macrophages. The effects of asperlin on the LPS-induced expression of iNOS and COX-2 and production of NO, PGE₂, TNF-α, and IL-1β were partially reversed by a HO-1 inhibitor, tin protoporphyrin. These findings suggest that asperlin-induced HO-1 expression plays a role in the anti-inflammatory effects of asperlin in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspergillus / metabolism*
  • Cell Line, Transformed
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism
  • Enzyme Inhibitors / pharmacology
  • Epoxy Compounds / adverse effects
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / isolation & purification
  • Epoxy Compounds / pharmacology*
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / metabolism*
  • I-kappa B Proteins / metabolism
  • Inflammation Mediators / metabolism
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Protein Transport / drug effects
  • Pyrones / adverse effects
  • Pyrones / chemistry
  • Pyrones / isolation & purification
  • Pyrones / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Epoxy Compounds
  • I-kappa B Proteins
  • Inflammation Mediators
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Nfkbia protein, mouse
  • Pyrones
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide
  • asperlin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2