Anti-BACE-1 activity of Three Constituents Identified in the Adults of Blattella germanica

Abstract

Alzheimer's disease (AD), acknowledged as progressive multifarious neurodegerative disorder, is the leading cause of presenile and senile dementia in both developed and developing countries. There are two hallmarks of AD, amyloid plaques and neurofibrillary tangles (NFTs). The human β-amyloid cleaving enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. AD is currently treated using acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. Until now, there is no cure for AD, and no treatments can stop or reverse its symptoms. Therefore, there is a pressing need to develop new, safe, improved naturally occurring anti-AD agents.

In this study, a fluorescence resonance energy transfer-based enzyme assay was used to identify the BACE-1 inhibitory constituents from methanol extracts from the adult German cockroach, Blattella germanica, L. (Blattodea: Ectobiidae). The active constituents were determined to be the polyunsaturated omega-6 fatty acid linoleic acid, the steroid cholest-5-en-3-ol, and the flavanonol fustin. Based on IC50 values, cholest-5-en-3-ol (21.13 μM) and linoleic acid (23.02 μM) were the most potent BACE-1 inhibitory constituents. The IC50 of fustin was 34.88 μM. Overall, these compounds were significantly less potent inhibitors of BACE-1 than either Inhibitor IV (IC50, 1.51 μM) or epigallocatechin gallate (IC50, 13.45 μM). German cockroach whole-body constituents containing cholest-5-en-3-ol, linoleic acid, and fustin are potential therapeutics or lead molecules for the prevention or treatment of AD.