Abstract
In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Mosher's method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-α, IL-1β and IL-6 production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro-inflammatory mediators and NF-κB DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation.
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 / chemistry*
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Anti-Inflammatory Agents / pharmacology
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Cells, Cultured
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Dinoprostone / antagonists & inhibitors
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Dinoprostone / metabolism
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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 / antagonists & inhibitors
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I-kappa B Proteins / metabolism
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / metabolism
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Interleukin-6 / antagonists & inhibitors
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Interleukin-6 / metabolism
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Lactones / chemistry
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Lactones / pharmacology
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / metabolism
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Mice
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Mice, Inbred C57BL
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NF-E2-Related Factor 2 / antagonists & inhibitors
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NF-E2-Related Factor 2 / metabolism
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / metabolism
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Penicillium / chemistry*
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Phosphorylation / drug effects
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents
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I-kappa B Proteins
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Interleukin-1beta
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Interleukin-6
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Lactones
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NF-E2-Related Factor 2
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NF-kappa B
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Nfkbia protein, mouse
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Tumor Necrosis Factor-alpha
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NF-KappaB Inhibitor alpha
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Nitric Oxide
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Heme Oxygenase-1
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Dinoprostone