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Neuroprotective γ-Pyrones from Fusarium Solani JS-0169: Cell-Based Identification of Active Compounds and an Informatics Approach to Predict the Mechanism of Action

1
College of Pharmacy, Duksung Women’s University, Seoul 01369, Korea
2
College of Korean Medicine, Gachon University, Seongnam 13120, Korea
3
Department of Physiology, College of Korean Medicine, Gachon University, Seongnam 13120, Korea
4
Biological Resources Assessment Division, National Institute of Biological Resources, Incheon 22689, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2020, 10(1), 91; https://doi.org/10.3390/biom10010091 (registering DOI)
Received: 16 December 2019 / Revised: 31 December 2019 / Accepted: 4 January 2020 / Published: 6 January 2020
Glutamate toxicity has been implicated in neuronal cell death in both acute CNS injury and in chronic diseases. In our search for neuroprotective agents obtained from natural sources that inhibit glutamate toxicity, an endophytic fungus, Fusarium solani JS-0169 isolated from the leaves of Morus alba, was found to show potent inhibitory activity. Chemical investigation of the cultures of the fungus JS-0169 afforded isolation of six compounds, including one new γ-pyrone (1), a known γ-pyrone, fusarester D (2), and four known naphthoquinones: karuquinone B (3), javanicin (4), solaniol (5), and fusarubin (6). To identify the protective effects of the isolated compounds (16), we assessed their inhibitory effect against glutamate-induced cytotoxicity in HT22 cells. Among the isolates, compound 6 showed significant neuroprotective activity on glutamate-mediated HT22 cell death. In addition, the informatics approach using in silico systems pharmacology identified that compound 6 may exert its neuroprotective effect by controlling the amount of ubiquinone. The results suggest that the metabolites produced by the endophyte Fusarium solani JS-0169 might be related to the neuroprotective activity of its host plant, M. alba. View Full-Text
Keywords: neuroprotection; Fusarium solani; endophyte; γ-pyrones; informatics approach neuroprotection; Fusarium solani; endophyte; γ-pyrones; informatics approach
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MDPI and ACS Style

Choi, H.G.; Song, J.H.; Park, M.; Kim, S.; Kim, C.-E.; Kang, K.S.; Shim, S.H. Neuroprotective γ-Pyrones from Fusarium Solani JS-0169: Cell-Based Identification of Active Compounds and an Informatics Approach to Predict the Mechanism of Action. Biomolecules 2020, 10, 91.

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