Inhibition Of Bace1 And Amyloid-Beta Aggregation By Meroterpenoids From The Mushroom Albatrellus Yasudae

To develop drugs to treat Alzheimer's disease (AD) on the basis of the amyloid cascade hypothesis, the amyloid-beta (A beta) aggregation inhibitory activities of 110 extracts from mushrooms were evaluated by thioflavin T (Th-T) assays. The MeOH extract of Albatrellus yasudae inhibited A beta aggregation, and the bioactivity-guided fractionation of the extract afforded four novel meroterpenoids, named scutigeric acid (1), albatrelactone methyl ester (2), albatrelactone (3), and 10',11'-dihydroxygrifolic acid (4), together with two known compounds, grifolin (5) and grifolic acid (6). The structures of 1-4 were elucidated using NMR, MS, UV, IR, and induced ECD spectral data. The structure of 1 was determined as a methyl ester (1a) by 2D NMR spectroscopy. Th-T assays showed that compounds 1-4 and la possessed inhibitory activities against A beta aggregation, with IC50 values of 6.6, 40.7, 51.4, 53.3, and 50.3 mu M, respectively. Notably, 1 possessed an inhibitory activity against A beta aggregation comparable to that of myricetin as a positive control. Moreover, 1-6 exhibited inhibitory activities against BACE1, with IC50 values of 1.6, 10.9, 10.5, 34.4, 6.1, and 1.4 mu M, respectively.