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Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia

Microglia play a significant role in immune defense and tissue repair in the central nervous system (CNS). Microglial activation and the resulting neuroinflammation play a key role in the pathogenesis of neurodegenerative disorders. Recently, inflammation reduction strategies in neurodegenerative di...

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Autores principales: Cao, Thao Quyen, Liu, Zhiming, Dong, Linsha, Lee, Hwan, Ko, Wonmin, Vinh, Le Ba, Tuan, Nguyen Quoc, Kim, Youn-Chul, Sohn, Jae Hak, Yim, Joung Han, Lee, Dong-Sung, Oh, Hyuncheol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103959/
https://www.ncbi.nlm.nih.gov/pubmed/35566201
http://dx.doi.org/10.3390/molecules27092851
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author Cao, Thao Quyen
Liu, Zhiming
Dong, Linsha
Lee, Hwan
Ko, Wonmin
Vinh, Le Ba
Tuan, Nguyen Quoc
Kim, Youn-Chul
Sohn, Jae Hak
Yim, Joung Han
Lee, Dong-Sung
Oh, Hyuncheol
author_facet Cao, Thao Quyen
Liu, Zhiming
Dong, Linsha
Lee, Hwan
Ko, Wonmin
Vinh, Le Ba
Tuan, Nguyen Quoc
Kim, Youn-Chul
Sohn, Jae Hak
Yim, Joung Han
Lee, Dong-Sung
Oh, Hyuncheol
author_sort Cao, Thao Quyen
collection PubMed
description Microglia play a significant role in immune defense and tissue repair in the central nervous system (CNS). Microglial activation and the resulting neuroinflammation play a key role in the pathogenesis of neurodegenerative disorders. Recently, inflammation reduction strategies in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the anti-neuroinflammatory potential of compounds from the Antarctic fungi strain Aspergillus sp. SF-7402 in lipopolysaccharide (LPS)-stimulated BV2 cells. Four metabolites were isolated from the fungi through chemical investigations, namely, 5-methoxysterigmatocystin (1), sterigmatocystin (2), aversin (3), and 6,8-O-dimethylversicolorin A (4). Their chemical structures were elucidated by extensive spectroscopic analysis and HR-ESI-MS, as well as by comparison with those reported in literature. Anti-neuroinflammatory effects of the isolated metabolites were evaluated by measuring the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in LPS-activated microglia at non-cytotoxic concentrations. Sterigmatocystins (1 and 2) displayed significant effects on NO production and mild effects on TNF-α and IL-6 expression inhibition. The molecular mechanisms underlying this activity were investigated using Western blot analysis. Sterigmatocystin treatment inhibited NO production via downregulation of inducible nitric oxide synthase (iNOS) expression in LPS-stimulated BV2 cells. Additionally, sterigmatocystins reduced nuclear translocation of NF-κB. These results suggest that sterigmatocystins present in the fungal strain Aspergillus sp. are promising candidates for the treatment of neuroinflammatory diseases.
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spelling pubmed-91039592022-05-14 Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia Cao, Thao Quyen Liu, Zhiming Dong, Linsha Lee, Hwan Ko, Wonmin Vinh, Le Ba Tuan, Nguyen Quoc Kim, Youn-Chul Sohn, Jae Hak Yim, Joung Han Lee, Dong-Sung Oh, Hyuncheol Molecules Article Microglia play a significant role in immune defense and tissue repair in the central nervous system (CNS). Microglial activation and the resulting neuroinflammation play a key role in the pathogenesis of neurodegenerative disorders. Recently, inflammation reduction strategies in neurodegenerative diseases have attracted increasing attention. Herein, we discovered and evaluated the anti-neuroinflammatory potential of compounds from the Antarctic fungi strain Aspergillus sp. SF-7402 in lipopolysaccharide (LPS)-stimulated BV2 cells. Four metabolites were isolated from the fungi through chemical investigations, namely, 5-methoxysterigmatocystin (1), sterigmatocystin (2), aversin (3), and 6,8-O-dimethylversicolorin A (4). Their chemical structures were elucidated by extensive spectroscopic analysis and HR-ESI-MS, as well as by comparison with those reported in literature. Anti-neuroinflammatory effects of the isolated metabolites were evaluated by measuring the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in LPS-activated microglia at non-cytotoxic concentrations. Sterigmatocystins (1 and 2) displayed significant effects on NO production and mild effects on TNF-α and IL-6 expression inhibition. The molecular mechanisms underlying this activity were investigated using Western blot analysis. Sterigmatocystin treatment inhibited NO production via downregulation of inducible nitric oxide synthase (iNOS) expression in LPS-stimulated BV2 cells. Additionally, sterigmatocystins reduced nuclear translocation of NF-κB. These results suggest that sterigmatocystins present in the fungal strain Aspergillus sp. are promising candidates for the treatment of neuroinflammatory diseases. MDPI 2022-04-29 /pmc/articles/PMC9103959/ /pubmed/35566201 http://dx.doi.org/10.3390/molecules27092851 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cao, Thao Quyen
Liu, Zhiming
Dong, Linsha
Lee, Hwan
Ko, Wonmin
Vinh, Le Ba
Tuan, Nguyen Quoc
Kim, Youn-Chul
Sohn, Jae Hak
Yim, Joung Han
Lee, Dong-Sung
Oh, Hyuncheol
Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia
title Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia
title_full Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia
title_fullStr Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia
title_full_unstemmed Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia
title_short Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402 via Regulating the NF-κB Signaling Pathway in Microglia
title_sort identification of potential anti-neuroinflammatory inhibitors from antarctic fungal strain aspergillus sp. sf-7402 via regulating the nf-κb signaling pathway in microglia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103959/
https://www.ncbi.nlm.nih.gov/pubmed/35566201
http://dx.doi.org/10.3390/molecules27092851
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