Bioassay-guided isolation of acetylcholinesterase and butyrylcholinesterase inhibitors from Horsfieldia tomentosa fruits (Myristicaceae)
Document Type
Article
Publication Date
2-1-2025
Abstract
Alzheimer's disease (AD) is the most common form of dementia associated with the accumulation of abnormal protein deposits in the brain, including beta-amyloid plaques and tau tangles, as well as oxidative stress. The limited effectiveness of current medications in temporarily treating symptoms has driven interest in natural products for their diverse biological activities. This study investigates the bioactive potential of various extracts obtained from the fruits of Horsfieldia tomentosa, focusing on their antioxidant and anticholinesterase properties. Total phenolic and flavonoid contents were quantified, antioxidant and anticholinesterase activities were evaluated. The ethyl acetate extract exhibited the highest bioactivity, with total flavonoid content (361.11 f 26.24 mg QE/g), total phenolic content (1601.46 f 1.23 mg GAE/g), antioxidant activity (1.81 f 0.06 mu g/L), and significant anticholinesterase activities (AChE = 6.0 f 0.30 mu g/mL; BuChE = 32.1 mu g/ mL). Three previously undescribed phenolic compounds along with four known compounds were purified from this extract. The assayed isolated compounds exhibit selective cholinesterase inhibition, with compound 2 showing the strongest activity (IC50 value of 3.9 mu M against AChE), while compound 1 was more effective against butyrylcholinesterase (IC50 value of 7.8 mu M). Molecular docking supported the in vitro findings, revealing binding energies of- 9.0 f 0.5,- 8.5 f 0.1, and- 8.3 f 0.1 kcal mol-1 for compounds 1 , 2 and 5 , respectively, against butyrylcholine protease (6ESY). Compound 1 also showed significant binding energy (8.0 f 0.1 kcal mol - 1) against acetylcholine protease (4MOE). In these results, compound 2 acts as a dual inhibitor, while compounds 1 and 5 primarily inhibit butyrylcholinesterase. These results underscore the therapeutic potential of Horsfieldia tomentosa in treating Alzheimer's disease.
Keywords
Alzheimer's disease, Horsfieldia tomentosa, Acetylcholinesterase, Butyrylcholinesterase, Molecular docking
Divisions
CHEMISTRY
Funders
Universiti Sains Malaysia [Grant No: R502-KR-ARP004-00AUPRM003-K134],Tertiary Education Trust Fund (TETFUND),CNRS-UM,Ministry of Higher Education, Research & Innovation, Oman [Grant No: FRGS/1/2023/STG04/USM/02/3]
Publication Title
Phytochemistry Letters
Volume
65
Publisher
Elsevier
Publisher Location
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS