Inhibition of amyloid β aggregation and BACE1, and protective effect on SH-SY5Y cells, by p-terphenyl compounds from mushroom Thelephora aurantiotincta

J Nat Med. 2025 Jan;79(1):268-277. doi: 10.1007/s11418-024-01865-4. Epub 2024 Nov 29.

Abstract

The number of patients with Alzheimer's disease (AD) is expected to increase as the population ages. The amyloid cascade hypothesis is proposed as the pathogenic mechanism of AD. We report the isolation and structural determination of three new p-terphenyl compounds, thelephantin P (1), thelephantin Q (2), and thelephantin R (3), with four known compounds (4-7), from the fruiting bodies of Thelephora aurantiotincta Corner. We evaluated Aβ aggregation and BACE1 inhibitory activities and neuroprotective activities of these isolated compounds. Compound 1 was shown to be multi-inhibitors for AD. Compound 1 had an IC50 = 12.9 μM (Aβ), 6.3 μM (BACE1), and EC50 = 8.0 μM (neuroprotection), respectively. Therefore, these compounds are potential therapeutic agents for AD.

Keywords: p-Terphenyl compounds; Alzheimer’s disease; Amyloid-beta; BACE1; Mushroom; Neuroprotection.

MeSH terms

  • Agaricales / chemistry
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid Precursor Protein Secretases* / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases* / metabolism
  • Amyloid beta-Peptides* / metabolism
  • Aspartic Acid Endopeptidases* / antagonists & inhibitors
  • Aspartic Acid Endopeptidases* / metabolism
  • Cell Line, Tumor
  • Humans
  • Molecular Structure
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / isolation & purification
  • Neuroprotective Agents* / pharmacology
  • Protein Aggregates / drug effects
  • Terphenyl Compounds / chemistry
  • Terphenyl Compounds / isolation & purification
  • Terphenyl Compounds / pharmacology

Substances

  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Peptides
  • Aspartic Acid Endopeptidases
  • Neuroprotective Agents
  • BACE1 protein, human
  • Terphenyl Compounds
  • Protein Aggregates