Inhibition of A β aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239

AbstractAlzheimer ’s disease (AD) is an important human disease that mainly causes cognitive impairments. Growing evidence has shown that amyloid-β (Aβ) peptide plays a key role in AD pathogenesis in what is known as the Aβ cascade hypothesis. This hypothesis suggests the importance of suppressing Aβ aggregatio n and Aβ production. The latter process is governed by β-site APP Cleaving Enzyme1 (BACE1) and γ-secretase. We, therefore, focused on Aβ aggregation inhibitory activity, initially assessing numerous extracts derived from our marine-derived fungus collections. One EtOAc extract derived from anAspergillus sp. exhibited A β aggregation inhibitory activity. Eleven known compounds (1–11) were isolated from CHCl3 and EtOAc extracts derived from the fungus, and the structures were identified based on MS, NMR, and ECD spectra. Compounds2,6, and10 inhibited A β aggregation with IC50 values of 2.8, 3.9, and 8.1  μM, respectively. The protective effect on SH-SY5Y cells against Aβ toxicity was also evaluated, and compounds6 and10 significantly alleviated A β toxicity. BACE1 inhibitory activity was also examined, and compounds4,5,7,10, and11 inhibited BACE1 activity with IC50 values of 14.9, 70.0, 36.5, 28.0, and 72.8  μM, respectively. These data suggest that compound10 could be useful in AD treatment.
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research