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

Abstract

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 (1–6), 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.

The Neuroprotective Potential of Endophytic Fungi and Proposed Molecular Mechanism: A Current Update

“…Additionally, the compound SSF2-2 increased the expression of Nrf2 and HO −1 pathways, whereas inhibited the apoptotic cell death via inhibition of cytochrome c and cleaved caspase-9, -3 in glutamate-induced HT22 cells [ 75 ]. Choi and co-workers, isolated and identified six neuroprotective bioactive compounds present in an endophytic fungi Fusarium solani JS-0169 collected from the leaves of Morus alba [ 76 ]. These six bioactive compounds, namely, ϒ-pyrone, fusarester D, karuquinone B, javanicin, solaniol, and fusarubin were identified via NMR spectroscopy analysis.…”

“…Among these compounds, ϒ-pyrone, javanicin, and fusarubin showed the acceptable neuroprotective activity in a dose-dependent manner. However, fusarubin at 12.5 µ M concentration displayed highest cell viability of 90.7 ± 4.5% in HT22 cells, it also possess strong DPPH scavenging activity [ 76 ].…”

Natural Polypropionates in 1999–2020: An Overview of Chemical and Biological Diversity

“…Three new simple 4-pyrone PPs, 96 – 98 , were isolated from Aspergillus versicolor , Acremonium citrinum and Fusarium solani , respectively [ 32 , 56 , 57 ]. 98 displayed a dose-dependent neuroprotective effect against glutamate-induced cytotoxicity in HT22 murine hippocampal neuronal cells.…”

“…The chemical investigation of the same species mollusk Siphonaria capensis led to isolation of a 2furanone-containing polypropionate capensifuranone (109) [9]. The all S configuration at the side chain was proposed by the same biosynthetic pathway with those of siphonarienfuranone and its Z- Three new simple 4-pyrone PPs, 96-98, were isolated from Aspergillus versicolor, Acremonium citrinum and Fusarium solani, respectively [32,56,57]. 98 displayed a dose-dependent neuroprotective effect against glutamate-induced cytotoxicity in HT22 murine hippocampal neuronal cells.…”

Luteapyrone, a Novel ƴ-Pyrone Isolated from the Filamentous Fungus Metapochonia lutea

“…FKI-1082 (Ascomycota, Hypocreales, Clavicipitaceae) [9]. The recent reports on description of new structurally related γ-pyrones, namely fusapyrones and fusaresters A-E are connected to fungal genus Fusarium (Ascomycota, Hypocreales, Nectriaceae) species [10][11][12] and acrepyrone A to endophytic fungus Acremonium citrinum SS-g13 [13].…”