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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / adverse effects
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Aspergillus / metabolism*
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Cell Line, Transformed
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cells, Cultured
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Cyclooxygenase 2 / chemistry
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Cyclooxygenase 2 / metabolism
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Enzyme Inhibitors / pharmacology
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Epoxy Compounds / adverse effects
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Epoxy Compounds / chemistry
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Epoxy Compounds / isolation & purification
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Epoxy Compounds / pharmacology*
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Heme Oxygenase-1 / antagonists & inhibitors
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Heme Oxygenase-1 / metabolism*
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I-kappa B Proteins / metabolism
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Inflammation Mediators / metabolism
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Macrophage Activation / drug effects
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Macrophages / drug effects*
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Macrophages / immunology
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Macrophages / metabolism*
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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NF-E2-Related Factor 2 / metabolism
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NF-KappaB Inhibitor alpha
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / antagonists & inhibitors
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Nitric Oxide Synthase Type II / metabolism
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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Protein Transport / drug effects
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Pyrones / adverse effects
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Pyrones / chemistry
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Pyrones / isolation & purification
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Pyrones / pharmacology*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Enzyme Inhibitors
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Epoxy Compounds
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I-kappa B Proteins
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Inflammation Mediators
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Membrane Proteins
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NF-E2-Related Factor 2
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Nfe2l2 protein, mouse
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Nfkbia protein, mouse
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Pyrones
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NF-KappaB Inhibitor alpha
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Nitric Oxide
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asperlin
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Heme Oxygenase-1
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Hmox1 protein, mouse
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Ptgs2 protein, mouse
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Cyclooxygenase 2