Anti-Alzheimer's disease potential of coumarins from Angelica decursiva and Artemisia capillaris and structure-activity analysis
10.1016/j.apjtm.2016.01.014
- Author:
Md. Yousof ALI
1
;
Susoma JANNAT
1
;
Anupom ROY
1
;
Jae Sue CHOI
1
;
Hyun Ah JUNG
2
;
Ran Joo CHOI
3
Author Information
1. Department of Food and Life Science, Pukyong National University
2. Department of Food Science and Human Nutrition, Chonbuk National University
3. Angiogenesis and Chinese Medicine Laboratory, Department of Pharmacology, University of Cambridge
- Publication Type:Journal Article
- Keywords:
BACE1;
Cholinesterase;
Coumarins;
Daphnetin;
Esculetin;
Umbelliferone 6-carboxylic acid
- From:
Asian Pacific Journal of Tropical Medicine
2016;9(2):103-111
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To use structure-activity analysis to study the anti-Alzheimer's disease (anti-AD) activity of natural coumarins isolated from Angelica decursiva and Artemisia capillaris, along with one purchased coumarin (daphnetin). Methods: Umbelliferone, umbelliferone 6-carboxylic acid, scopoletin, isoscopoletin, 7-methoxy coumarin, scoparone, scopolin, and esculetin have been previously isolated; however 2'-isopropyl psoralene was isolated from Angelica decursiva for the first time to evaluate their inhibitory effects against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) enzyme activity. We scrutinized the potentials of coumarins as cholinesterase and BACE1 inhibitors via enzyme kinetics and molecular docking simulation. Results: Among the test compounds, umbelliferone 6-carboxylic acid, esculetin and daphnetin exhibited potent inhibitory activity against AChE, BChE and BACE1. Both esculetin and daphnetin have a catechol group and exhibit significant anti-AD activity against AChE and BChE. In contrast, presence of a sugar moiety and methoxylation markedly reduced the anti-AD activity of the coumarins investigated in this study. With respect to BACE1 inhibition, umbelliferone 6-carboxylic acid, esculetin and daphnetin contained carboxyl or catechol groups, which significantly contributed to their anti-AD activities. To further investigate these results, we generated a 3D structure of BACE1 using Autodock 4.2 and simulated binding of umbelliferone 6-carboxylic acid, esculetin and daphnetin. Docking simulations showed that different residues of BACE1 interacted with hydroxyl and carboxylic groups, and the binding energies of umbelliferone 6-carboxylic acid, esculetin and daphnetin were negative (-4.58, -6.25 and -6.37 kcal/mol respectively). Conclusions: Taken together, our results suggest that umbelliferone 6-carboxylic acid, esculetin and daphnetin have anti-AD effects by inhibiting AChE, BChE and BACE1, which might be useful against AD.
