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Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer’s disease. In this paper, the combined bioassay model of acetylcholinesterase (AChE) inhibition, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, and Artemia larval lethality was used to evaluate the activity and toxicity of 35 marine fungal strains from seas around China. Their bioactive constituents were revealed by thin layer chromatography (TLC) autography, bioactivity coupled LC–MS/MS and Global Natural Products Social Molecular Networking (GNPS). The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound, ‘tacrine’, for which the ratio was 89.8% at 200 μg/ml. Six strains displayed both AChE inhibition (inhibition ratios > 20% at 200 μg/ml) and DPPH scavenging activity (scavenging ratios > 30% at 200 μg/ml) together with low Artemia larval toxicity (lethal rates Talaromyces sp. C21-1, Aspergillus terreus C23-3, Trichoderma harzianum DLEN2008005, and Penicillium corylophilum TBG1-17. From the most potent sample F-11-1-b (derived from Aspergillus terreus C23-3), five AChE inhibitors and seven antioxidants were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC–MS/MS, and LC–MS/MS coupled with DPPH incubation. Furthermore, with the aid of GNPS, the AChE inhibitors were plausibly annotated as territrem analogues including territrems A–C/D, arisugacin A and an unknown compound 4, and the seven antioxidants were assigned as butyrolactone Ι, aspernolide E, a phenolic derivative and possibly unknown compounds 8–10 and 12.

A new isoflavone derivative compound 1 (psoralenone) was isolated from soybean inoculated with a marine fungus Aspergillus terreus C23-3, together with seven known compounds including isoflavones 2–6, butyrolactone I (7) and blumenol A (8). Their structures were elucidated by MS, NMR, and ECD. Psoralenone displayed moderate in vitro anti-inflammatory activity in the LPS-induced RAW264.7 cell model. Compound 2 (genistein) showed moderate acetylcholinesterase (AChE) inhibitory activity whereas compounds 2, 5 (biochanin A), 6 (psoralenol), and 7 exhibited potent larvicidal activity against brine shrimp. Compounds 3 (daidzein), 4 (4ʹ-hydroxy-6,7-dimethoxyisoflavone), and 5–7 showed broad-spectrum anti-microbial activity, and compound 7 also showed moderate 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity.

Additional file 1. Physicochemical properties of BTL-I through online prediction tool of ADMETlab 2.0.

BackgroundMounting evidences indicate that oxidative stress and neuroinflammation are related to neurodegenerative disorders (NDs). Butyrolactone I (BTL-I), a marine fungal metabolite, was previously reported as an in-vitro neuroprotectant and inflammation inhibitor. However, little is known about its in-vivo effects. Zebrafish (Danio rerio) could be used as a convenient model in evaluation of toxicology and central nervous system (CNS) diseases. MethodsHere, we employ the in-vivo and in-silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established cognitive deficits model in zebrafish by intraperitoneal (i.p.) injection of AlCl3 (21 μg), and assessed their behaviors in the T-maze test. Proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well as acetylcholinesterase (AChE) activity, glutathione (GSH) levels were assayed 24 h after the AlCl3 injection. The intestinal flora of the zebrafish were investigated by 16 S rDNA high-throughput analysis. A marine fungal metabolite, butyrolactone I (BTL-I) was used to modulate zebrafish cognitive deficits evoked by AlCl3. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by in-silico tool of ADMETlab.ResultsBTL-I dose-dependently ameliorated AlCl3-induced cognitive deficits in zebrafish. While, AlCl3 treatment elevated the levels of central and peripheral proinflammatory cytokines, increased AChE activity, and lowered GSH in the brain of zebrafish, these effects except GSH reducing were reversed by 25–100 mg/kg BTL-I administration. 16S rDNA high-throughput sequencing of intestinal flora of zebrafish showed that AlCl3 decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacterial while BTL-I contributed to maintain the predominance of beneficial Gram-positive bacteria. The in-silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles.ConclusionsThe present findings suggest BTL-I as a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance.