4-O-galloylalbiflorin discovered from Paeonia lactiflora Pall. is a potential β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor. (December 2016)

• Record Type: Journal Article
• Authors: Hu, Xiao-Long; Li, Ye-Bo; Qi, Song; Zhang, Qiao; Ren, Tian-Shu; Meng, Wei-Hong; Zhao, Qing-Chun
• Is Part Of: Journal of functional foods. Volume 27(2016)
• Page Start: 517
• Page End: 525
• Publication Date: 2016-12
• Subjects: Alzheimer's disease (AD) -- β-secretase (BACE1) -- β-amyloid peptide -- Paeonia lactiflora Pall -- 4-O-galloylalbiflorin -- Docking; Aβ β-amyloid peptide -- AD Alzheimer's disease -- APP amyloid precursor protein -- BACE1 β-site amyloid precursor protein cleaving enzyme 1 -- BBB blood–brain barrier -- DS 3.0 Discovery studio 3.0 -- FRET florescence resonance energy transfer -- HIF-1α Hypoxia-inducible factor 1α -- 4-O-GA 4-O-galloylalbiflorin; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2016.10.012
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: 4-O-galloylalbiflorin (4-O-GA) was discovered as a novel BACE1 inhibitor. 4-O-GA could selectively inhibit the activity of BACE1 with IC50 5.11 ± 0.73 µM. 4-O-GA could decrease Aβ1–40 and Aβ1–42 levels in SH-SY5Y cells. Docking results showed 4-O-GA can well bind with key residues of BACE1. Abstract: β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the formation of β-amyloid peptides (Aβ), which are important in the development of Alzheimer's disease. It has been demonstrated that albiflorin can alleviate Aβ aggregation. However, the mechanism behind this effect is unknown. In our previous work, albiflorin and its four analogues were isolated from Paeonia lactiflora Pall. This study aims to investigate the relationship of these four compounds with BACE1. Our results show that the albiflorin analogue 4-O-galloylalbiflorin (4-O-GA) had the strongest BACE1 inhibitory effect and was also selective for BACE1. Furthermore, docking study of BACE1 with these analogues yielded similar results, whereby 4-O-GA treatment caused the greatest decreases in both the generation of Aβ1–42 and Aβ1–40 and in the expression of BACE1 and HIF-1α. Our findings indicate that 4-O-GA exerted significant and selective inhibitory activities against BACE1, potentially providing a useful agent for developing BACE1 inhibitor drugs.