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

Five compounds were isolated from the fermentation broth of the oyster endophytic fungus <i>Penicillium griseofulvum</i> QDYM-3, including 1,6-dihydroxy-3-methoxy-8-methylxanthone (<b>1</b>), (+)-griseofulvin (<b>2</b>), (4 <i>R</i>,5<i>R</i>,6<i>R</i>)-4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-methyl-2-cyclohexen-1-one (<b>3</b>), 3-hydroxybenzyl alcohol (<b>4</b>), and epigriseofulvin (<b>5</b>). Compounds (<b>1</b>), (<b>3</b>), and (<b>4</b>) significantly inhibited Aβ aggregation, with compound (<b>3</b>) being the most effective, after the compound (<b>3</b>) 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 (<b>3</b>) 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.