Comparative metabolomics of acetylcholinesterase and α-glucosidase inhibitors in pericarp of Garcinia mangostana L.
Journal
Botanical Studies
Journal Volume
66
Journal Issue
1
Start Page
Article number 13
ISSN
1999-3110
Date Issued
2025-05-21
Author(s)
Wang, Yun-Han
Liu, Ta-Wei
Hsiao, Sui-Wen
Chu, Man-Hsiu
Hsu, Su-Jung
Chen, Shih Yin
Lee, Ching-Kuo
Abstract
Background
Mangosteen (Garcinia mangostana L.) pericarp extract has demonstrated potential against Alzheimer’s disease (AD) and diabetes mellitus (DM). This study introduces a rapid dereplication and comparative approach to identify and characterize acetylcholinesterase (AChE) and α-glucosidase inhibitors in mangosteen pericarp. Using protein-subtraction, MS profiling, and computational modeling is effective for screening, identifying, and analyzing enzyme-inhibiting compounds from plant sources, and quantitative analysis of the main components has been performed.
Results
The Mangosteen pericarp extract observed significant inhibitory activity against α-glucosidase and AChE, with IC50 values of 31.02 and 70.56 µg/mL, respectively. By comparing profiles of protein-subtracted extracts with non-treated extracts, eight potential inhibitors for each enzyme were identified: 8-desoxygartanin, gartanin, 3-isomangostin, β-mangostin, 9-hydroxycalabaxanthone, γ-mangostin, α-mangostin, and garcinone E. The α-mangostin was the most abundant, comprising 39.589% of the extract. Molecular docking revealed these inhibitors target the peripheral anionic site of AChE and the active site of α-glucosidase, forming key hydrogen bonds and pi-pi stacking interactions.
Conclusion
This study emphasizes mangosteen pericarp as a promising natural source of these inhibitors, with potential for use in developing nutraceuticals and pharmaceuticals. The study validated a systems biology approach by applying dereplication and comparative UPLC-ESI-MS/MS metabolomics profiling to identify target-binding molecules in both protein-treated and untreated plant extracts. Further confirmation was obtained through molecular docking predictions, mechanism analysis, and compound quantification assays.
Subjects
Acetylcholinesterase
Comparative metabolomics
Dereplication
Mangosteen (Garciniaman gostana L)
α-glucosidase
SDGs
Publisher
Springer Science and Business Media LLC
Type
journal article