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

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.