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

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.

Inhibitory Effects of Ehretia tinifolia Extract on the Excessive Oxidative and Inflammatory Responses in Lipopolysaccharide-Stimulated Mouse Kupffer Cells

“…Compound methyl rosmarinate was identified at m/z 374, as previously reported in E. tinifolia ethyl acetate portion [26], and was known for its antioxidant and antifungal activities [22,27]. For the identification of the remaining compounds, the m/z values of the molecular ion [M-H] − and [M + HCOO] − were compared with the Waters Unifi Software Traditional Medicine Library (Waters Corporation, Milford, MA, USA) and corroborated from the previously reported literature [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. Among these compounds, schisantherin A, kaempferol-3,7diglucoside, procyanidin A2, and tocopherol exert anti-inflammatory and antioxidant activity and promote reproductive functions [43][44][45][46], which explain the potent antioxidant and anti-inflammatory activity observed in E. tinifolia.…”

The Biosynthesis, Structure Diversity and Bioactivity of Sterigmatocystins and Aflatoxins: A Review

“…Both compounds inhibited NO production by down-regulating the expression of inducible nitric oxide synthase (iNOS) and also reduced the nuclear translocation of NF-κB. These experimental results suggested that these two compounds are promising candidates for the treatment of neuroinflammatory diseases [ 60 ].…”