# Comparative metabolomics of acetylcholinesterase and α-glucosidase inhibitors in pericarp of Garcinia mangostana L

## TL;DR

This study identifies compounds in mangosteen pericarp that inhibit enzymes linked to Alzheimer's and diabetes, supporting its potential for drug development.

## Contribution

A novel systems biology approach combining dereplication and metabolomics profiling to identify enzyme inhibitors in plant extracts.

## Key findings

- Mangosteen pericarp extract inhibits AChE and α-glucosidase with IC50 values of 70.56 and 31.02 µg/mL, respectively.
- Eight potential inhibitors were identified, with α-mangostin being the most abundant at 39.589% of the extract.
- Molecular docking confirmed key interactions between inhibitors and enzyme sites, including hydrogen bonds and pi-pi stacking.

## Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s40529-025-00460-4.