Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123
A chemical investigation of the marine-derived fungal strain Penicillium glabrum (SF-7123) revealed a new citromycetin (polyketide) derivative ( 1 ) and four known secondary fungal metabolites, i.e, neuchromenin ( 2 ), asterric acid ( 3 ), myxotrichin C ( 4 ), and deoxyfunicone ( 5 ). The structures...
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ftdoajarticles:oai:doaj.org/article:bbff1d6c21bf4c598f6105f3d539876e 2023-05-15T14:01:58+02:00 Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123 Tran Minh Ha Dong-Cheol Kim Jae Hak Sohn Joung Han Yim Hyuncheol Oh 2020-05-01T00:00:00Z https://doi.org/10.3390/md18050247 https://doaj.org/article/bbff1d6c21bf4c598f6105f3d539876e EN eng MDPI AG https://www.mdpi.com/1660-3397/18/5/247 https://doaj.org/toc/1660-3397 doi:10.3390/md18050247 1660-3397 https://doaj.org/article/bbff1d6c21bf4c598f6105f3d539876e Marine Drugs, Vol 18, Iss 247, p 247 (2020) marine-derived fungi anti-inflammation anti-neuroinflammation PTP1B Biology (General) QH301-705.5 article 2020 ftdoajarticles https://doi.org/10.3390/md18050247 2022-12-30T23:45:53Z A chemical investigation of the marine-derived fungal strain Penicillium glabrum (SF-7123) revealed a new citromycetin (polyketide) derivative ( 1 ) and four known secondary fungal metabolites, i.e, neuchromenin ( 2 ), asterric acid ( 3 ), myxotrichin C ( 4 ), and deoxyfunicone ( 5 ). The structures of these metabolites were identified primarily by extensive analysis of their spectroscopic data, including NMR and MS data. Results from the initial screening of anti-inflammatory effects showed that 2 , 4 , and 5 possessed inhibitory activity against the excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC 50 values of 2.7 µM, 28.1 µM, and 10.6 µM, respectively. Compounds 2 , 4 , and 5 also inhibited the excessive production of NO, with IC 50 values of 4.7 µM, 41.5 µM, and 40.1 µM, respectively, in LPS-stimulated RAW264.7 macrophage cells. In addition, these compounds inhibited LPS-induced overproduction of prostaglandin E 2 in both cellular models. Further investigation of the most active compound ( 2 ) revealed that these anti-inflammatory effects were associated with a suppressive effect on the over-expression of inducible nitric oxide synthase and cyclooxygenase-2. Finally, we showed that the anti-inflammatory effects of compound 2 were mediated via the downregulation of inflammation-related pathways such as those dependent on nuclear factor kappa B and p38 mitogen-activated protein kinase in LPS-stimulated BV2 and RAW264.7 cells. In the evaluation of the inhibitory effects of the isolated compounds on protein tyrosine phosphate 1B (PTP1B) activity, compound 4 was identified as a noncompetitive inhibitor of PTP1B, with an IC 50 value of 19.2 µM, and compound 5 was shown to inhibit the activity of PTP1B, with an IC 50 value of 24.3 µM, by binding to the active site of the enzyme. Taken together, this study demonstrates the potential value of marine-derived fungal isolates as a bioresource for bioactive compounds. Article in Journal/Newspaper Antarc* Antarctic Directory of Open Access Journals: DOAJ Articles Antarctic The Antarctic Marine Drugs 18 5 247 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
marine-derived fungi anti-inflammation anti-neuroinflammation PTP1B Biology (General) QH301-705.5 |
spellingShingle |
marine-derived fungi anti-inflammation anti-neuroinflammation PTP1B Biology (General) QH301-705.5 Tran Minh Ha Dong-Cheol Kim Jae Hak Sohn Joung Han Yim Hyuncheol Oh Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123 |
topic_facet |
marine-derived fungi anti-inflammation anti-neuroinflammation PTP1B Biology (General) QH301-705.5 |
description |
A chemical investigation of the marine-derived fungal strain Penicillium glabrum (SF-7123) revealed a new citromycetin (polyketide) derivative ( 1 ) and four known secondary fungal metabolites, i.e, neuchromenin ( 2 ), asterric acid ( 3 ), myxotrichin C ( 4 ), and deoxyfunicone ( 5 ). The structures of these metabolites were identified primarily by extensive analysis of their spectroscopic data, including NMR and MS data. Results from the initial screening of anti-inflammatory effects showed that 2 , 4 , and 5 possessed inhibitory activity against the excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC 50 values of 2.7 µM, 28.1 µM, and 10.6 µM, respectively. Compounds 2 , 4 , and 5 also inhibited the excessive production of NO, with IC 50 values of 4.7 µM, 41.5 µM, and 40.1 µM, respectively, in LPS-stimulated RAW264.7 macrophage cells. In addition, these compounds inhibited LPS-induced overproduction of prostaglandin E 2 in both cellular models. Further investigation of the most active compound ( 2 ) revealed that these anti-inflammatory effects were associated with a suppressive effect on the over-expression of inducible nitric oxide synthase and cyclooxygenase-2. Finally, we showed that the anti-inflammatory effects of compound 2 were mediated via the downregulation of inflammation-related pathways such as those dependent on nuclear factor kappa B and p38 mitogen-activated protein kinase in LPS-stimulated BV2 and RAW264.7 cells. In the evaluation of the inhibitory effects of the isolated compounds on protein tyrosine phosphate 1B (PTP1B) activity, compound 4 was identified as a noncompetitive inhibitor of PTP1B, with an IC 50 value of 19.2 µM, and compound 5 was shown to inhibit the activity of PTP1B, with an IC 50 value of 24.3 µM, by binding to the active site of the enzyme. Taken together, this study demonstrates the potential value of marine-derived fungal isolates as a bioresource for bioactive compounds. |
format |
Article in Journal/Newspaper |
author |
Tran Minh Ha Dong-Cheol Kim Jae Hak Sohn Joung Han Yim Hyuncheol Oh |
author_facet |
Tran Minh Ha Dong-Cheol Kim Jae Hak Sohn Joung Han Yim Hyuncheol Oh |
author_sort |
Tran Minh Ha |
title |
Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123 |
title_short |
Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123 |
title_full |
Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123 |
title_fullStr |
Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123 |
title_full_unstemmed |
Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123 |
title_sort |
anti-inflammatory and protein tyrosine phosphatase 1b inhibitory metabolites from the antarctic marine-derived fungal strain penicillium glabrum sf-7123 |
publisher |
MDPI AG |
publishDate |
2020 |
url |
https://doi.org/10.3390/md18050247 https://doaj.org/article/bbff1d6c21bf4c598f6105f3d539876e |
geographic |
Antarctic The Antarctic |
geographic_facet |
Antarctic The Antarctic |
genre |
Antarc* Antarctic |
genre_facet |
Antarc* Antarctic |
op_source |
Marine Drugs, Vol 18, Iss 247, p 247 (2020) |
op_relation |
https://www.mdpi.com/1660-3397/18/5/247 https://doaj.org/toc/1660-3397 doi:10.3390/md18050247 1660-3397 https://doaj.org/article/bbff1d6c21bf4c598f6105f3d539876e |
op_doi |
https://doi.org/10.3390/md18050247 |
container_title |
Marine Drugs |
container_volume |
18 |
container_issue |
5 |
container_start_page |
247 |
_version_ |
1766272029219094528 |