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- Title
PTP1B Inhibitory and Anti-Inflammatory Effects of Secondary Metabolites Isolated from the Marine-Derived Fungus Penicillium sp. JF-55.
- Authors
Lee, Dong-Sung; Jang, Jae-Hyuk; Wonmin Ko; Kim, Kyoung-Su; Jae Hak Sohn; Kang, Myeong-Suk; Jong Seog Ahn; Kim, Youn-Chul; Hyuncheol Oh
- Abstract
Protein tyrosine phosphatase 1B (PTP1B) plays a major role in the negative regulation of insulin signaling, and is thus considered as an attractive therapeutic target for the treatment of diabetes. Bioassay-guided investigation of the methylethylketone extract of marine-derived fungus Penicillium sp. JF-55 cultures afforded a new PTP1B inhibitory styrylpyrone-type metabolite named penstyrylpyrone (1), and two known metabolites, anhydrofulvic acid (2) and citromycetin (3). Compounds 1 and 2 inhibited PTP1B activity in a dose-dependent manner, and kinetic analyses of PTP1B inhibition suggested that these compounds inhibited PTP1B activity in a competitive manner. In an effort to gain more biological potential of the isolated compounds, the anti-inflammatory effects of compounds 1-3 were also evaluated. Among the tested compounds, only compound 1 inhibited the production of NO and PGE2, due to the inhibition of the expression of iNOS and COX-2. Penstyrylpyrone (1) also reduced TNF-a and IL-1ß production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of I?B-a, NF-?B nuclear translocation, and NF-?B DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of penstyrylpyrone (1) on the pro-inflammatory mediators and NF-?B DNA binding activity were associated with the HO-1 expression. Therefore, these results suggest that penstyrylpyrone (1) suppresses PTP1B activity, as well as the production of pro-inflammatory mediators via NF-?B pathway, through expression of anti-inflammatory HO-1.
- Subjects
PENICILLIUM; MARINE fungi; PROTEIN-tyrosine phosphatase; ANTI-inflammatory agents; MARINE metabolites; PHOSPHORYLATION
- Publication
Marine Drugs, 2013, Vol 11, Issue 4, p1409
- ISSN
1660-3397
- Publication type
Article
- DOI
10.3390/md11041409