Research on secondary metabolites of the oyster endophytic fungus Penicillium griseofulvum QDYM-3 and their anti-Alzheimer’s disease activity

Five compounds were isolated from the fermentation broth of the oyster endophytic fungus Penicillium griseofulvum QDYM-3, including 1,6-dihydroxy-3-methoxy-8-methylxanthone (1), (+)-griseofulvin (2), (4 R,5R,6R)-4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-methyl-2-cyclohexen-1-one (3), 3-hydroxybenzyl alcohol (4), and epigriseofulvin (5). Compounds (1), (3), and (4) significantly inhibited Aβ aggregation, with compound (3) being the most effective, after the compound (3) was incubated with Aβ for 9 h, the THT fluorescence was detected to be 1089.67 AU, close to the 1044.33 AU of the positive control. Its neuroprotective effects were evaluated using an Aβ_1-42 induced SH-SY5Y cell injury model, showing no cytotoxicity at concentrations of 1 to 25 µg/mL. Notably, 1 µg/mL of compound (3) reduced ROS levels by 26.87%, the enzymatic activities of SOD, CAT, and GSH were elevated by 13.97%, 20.74%, and 82.27% respectively, while the level of MDA was reduced by 20.42%. Additionally, the expression of intracellular proteins p-Akt, p-GSK-3β and β-catenin were up-regulated by 57.9%, 50.8% and 40.4%, respectively, at a sample concentration of 5 μg/ml compared with the injury group.