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Identification of Potential Anti-Neuroinflammatory Inhibitors from Antarctic Fungal Strain Aspergillus sp. SF-7402
Thao Quyen Cao1,2, Zhiming Liu3, Linsha Dong3
1Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea.
Abstract:
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.
Insights
Compounds from Antarctic fungi, sterigmatocystins, show potential for treating neuroinflammatory diseases by reducing nitric oxide and inflammatory markers in microglia.
Area of Science:
- Neuroscience
- Pharmacology
- Mycology
Background:
- Microglia are crucial for CNS immune defense and repair.
- Neuroinflammation driven by microglial activation is implicated in neurodegenerative diseases.
- Developing anti-neuroinflammatory strategies is a key research area.
Purpose of the Study:
- To investigate the anti-neuroinflammatory potential of compounds from Antarctic fungus *Aspergillus* sp. SF-7402.
- To isolate and characterize metabolites from the fungal strain.
- To evaluate the effects of isolated compounds on lipopolysaccharide (LPS)-stimulated microglia.
Main Methods:
- Isolation and structural elucidation of four metabolites: 5-methoxysterigmatocystin (1), sterigmatocystin (2), aversin (3), and 6,8-O-dimethylversicolorin A (4).
- Assessment of anti-neuroinflammatory effects by measuring nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) production in LPS-activated BV2 cells.
- Investigation of molecular mechanisms using Western blot analysis to examine inducible nitric oxide synthase (iNOS) expression and NF-κB translocation.
Main Results:
- Sterigmatocystins (1 and 2) significantly inhibited NO production.
- Sterigmatocystins demonstrated mild inhibition of TNF-α and IL-6 expression.
- Sterigmatocystin treatment reduced iNOS expression and NF-κB nuclear translocation in LPS-stimulated BV2 cells.
Conclusions:
- Sterigmatocystins from *Aspergillus* sp. possess significant anti-neuroinflammatory properties.
- These compounds modulate key inflammatory pathways, including NO production and NF-κB signaling.
- Sterigmatocystins represent promising therapeutic candidates for neuroinflammatory diseases.
