PTP1B Inhibitory and Anti-Inflammatory Effects of Secondary Metabolites Isolated from the Marine-Derived Fungus Penicillium sp. JF-55
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-α and IL-1β 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), an inhibitor of HO-1, it was verified that the inhibitory effects of penstyrylpyrone (1) on the pro-inflammatory mediators and NF-κB 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-κB pathway, through expression of anti-inflammatory HO-1. View Full-Text
Figure 1
Supplementary materials
- Supplementary File 1:
Supplementary Information (PDF, 1167 KB)
- Supplementary File 2:
3D structure (MOL, 2 KB)
Display in MOL Viewer
3D structure generated by CORINA by Molecular Networks. - Supplementary File 3:
MOL-Document (MOL, 2 KB)
Display in MOL Viewer
- Supplementary File 4:
3D structure (MOL, 2 KB)
Display in MOL Viewer
3D structure generated by CORINA by Molecular Networks. - Supplementary File 5:
MOL-Document (MOL, 2 KB)
Display in MOL Viewer
- Supplementary File 6:
3D structure (MOL, 2 KB)
Display in MOL Viewer
3D structure generated by CORINA by Molecular Networks. - Supplementary File 7:
MOL-Document (MOL, 2 KB)
Display in MOL Viewer
Share & Cite This Article
Lee, D.-S.; Jang, J.-H.; Ko, W.; Kim, K.-S.; Sohn, J.H.; Kang, M.-S.; Ahn, J.S.; Kim, Y.-C.; Oh, H. PTP1B Inhibitory and Anti-Inflammatory Effects of Secondary Metabolites Isolated from the Marine-Derived Fungus Penicillium sp. JF-55. Mar. Drugs 2013, 11, 1409-1426.