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

J Nat Prod. 2021 Jun 25;84(6):1748-1754. doi: 10.1021/acs.jnatprod.0c01329. Epub 2021 Jun 8.

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 Albatrellus yasudae inhibited Aβ 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 1a possessed inhibitory activities against Aβ aggregation, with IC50 values of 6.6, 40.7, 51.4, 53.3, and 50.3 μM, respectively. Notably, 1 possessed an inhibitory activity against Aβ 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 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / chemistry
  • Alzheimer Disease / drug therapy
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Basidiomycota / chemistry*
  • Humans
  • Japan
  • Molecular Structure
  • Terpenes / isolation & purification
  • Terpenes / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Terpenes
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human