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

• Published in: Molecules
• Main Authors: Thao Quyen Cao, Zhiming Liu, Linsha Dong, Hwan Lee, Wonmin Ko, Le Ba Vinh, Nguyen Quoc Tuan, Youn-Chul Kim, Jae Hak Sohn, Joung Han Yim, Dong-Sung Lee, Hyuncheol Oh
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2022
• Subjects: Antarctica; fungi metabolites; neuroinflammation; BV2 cells; sterigmatocystin; NF-κB; Organic chemistry; QD241-441; Antarctic; The Antarctic; Antarc*
• Online Access: https://doi.org/10.3390/molecules27092851; https://doaj.org/article/bd5deb4312f548b789c7a8b3cd44928b

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.