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

Molecules

Jae Hak Sohn¹  Dong-Sung Lee²  Hwan Lee²  Zhiming Liu²  Wonmin Ko²  Linsha Dong²  Joung Han Yim³  Thao Quyen Cao⁴  Nguyen Quoc Tuan⁴  Youn-Chul Kim⁴  Le Ba Vinh⁴  Hyuncheol Oh⁴ 

[1] College of Medical and Life Sciences, Silla University, Busan 46958, Korea;College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, Korea;Division of Polar Life Sciences, Korea Polar Research Institute, Incheon 21990, Korea;Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea;

关键词: Antarctica;    fungi metabolites;    neuroinflammation;    BV2 cells;    sterigmatocystin;    NF-κB;   

DOI  :  10.3390/molecules27092851

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown