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.
Highlights
Prolonged inflammation can lead to a variety of diseases, including arthritis, inflammatory bowel disease, neurodegenerative disorders, and septic shock syndrome
In our ongoing studies on bioactive secondary metabolites from marine microorganisms from Korea [21,22,26,27], we investigated the chemical constituents of the extracts obtained from cultures of the marine-derived fungus Penicillium sp
Penicillinolide A (1) (Figure 1) was assigned the molecular formula C14H24O5 on the basis of HRESIMS data (m/z 295.1517 [M + Na]+), which was fully supported by the 1H and 13C NMR data (Table 1)
Summary
Prolonged inflammation can lead to a variety of diseases, including arthritis, inflammatory bowel disease, neurodegenerative disorders, and septic shock syndrome. Studies have shown that HO-1 expression inhibits the production of pro-inflammatory cytokines and chemokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in activated macrophages [5,6,7,8]. HO-1 inhibits iNOS expression and NO production in activated macrophages through inactivation of nuclear factor (NF)-κB [10,11,12,13,14]. Recent study has shown that natural products can activate Nrf by directly binding to Keap through a covalent linkage, which results in the induction of cytoprotective proteins including HO-1 [20]. Our previous studies on the metabolites from marine-derived fungi have resulted in the identification of HO-1 regulating activity and the investigation of the mechanism of the pharmacological activities related to anti-inflammatory activity [21,22]. This study led to the isolation of a new 10-membered lactone type metabolite, named penicillinolide A (1)
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