Inhibition of BACE1 and Amyloid-β Aggregation by Meroterpenoids from the Mushroom Albatrellus yasudae

Journal of Natural Products
2021.0

Abstract

To develop drugs to treat Alzheimer's disease (AD) on the basis of the amyloid cascade hypothesis, the amyloid-β (Aβ) aggregation inhibitory activities of 110 extracts from mushrooms were evaluated by thioflavin T (Th-T) assays. The MeOH extract of <i>Albatrellus yasudae</i> inhibited Aβ aggregation, and the bioactivity-guided fractionation of the extract afforded four novel meroterpenoids, named scutigeric acid (<b>1</b>), albatrelactone methyl ester (<b>2</b>), albatrelactone (<b>3</b>), and 10',11'-dihydroxygrifolic acid (<b>4</b>), together with two known compounds, grifolin (<b>5</b>) and grifolic acid (<b>6</b>). The structures of <b>1</b>-<b>4</b> were elucidated using NMR, MS, UV, IR, and induced ECD spectral data. The structure of <b>1</b> was determined as a methyl ester (<b>1a</b>) by 2D NMR spectroscopy. Th-T assays showed that compounds <b>1</b>-<b>4</b> and <b>1a</b> possessed inhibitory activities against Aβ aggregation, with IC<sub>50</sub> values of 6.6, 40.7, 51.4, 53.3, and 50.3 μM, respectively. Notably, <b>1</b> possessed an inhibitory activity against Aβ aggregation comparable to that of myricetin as a positive control. Moreover, <b>1</b>-<b>6</b> exhibited inhibitory activities against BACE1, with IC<sub>50</sub> values of 1.6, 10.9, 10.5, 34.4, 6.1, and 1.4 μM, respectively.

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