Integrative metabolomics, molecular networking and in silico analysis reveal bioactive antiplasmodial fractions from Aloe rigens
4 affiliations
- 1Centre d’Étude et de Recherche de Djibouti, Institut de Recherche Médicinale, Route de l’aéroport, Djibouti
- 2Unité Molécules de Communication et Adaptation des Microorganismes (MCAM
- 3Muséum National D’histoireNaturelle, CNRS
- 4INRAE
Abstract
Aloe rigens Reynolds & Bally (Asphodelaceae) is widely used in traditional medicine against malaria and demonstrated potent biological activity in our previous study. Despite its traditional use, its specific chemical and biological properties have not yet been comprehensively investigated. This study aimed to identify the phytochemical constituents responsible for the antiplasmodial activity of this plant through an integrated bioguided fractionation, untargeted metabolomics, and computational approach. Bioguided fractionation of Aloe rigens leaf extracts was conducted against Plasmodium falciparum (FcB-1 strain) using the SYBR Green fluorescence assay. The bioactive dichloromethane (RD) and ethyl acetate (RE) sub-extracts were profiled by LC-HRMS/MS and GC-MS. Untargeted metabolomic analysis, combining molecular networking (GNPS) with multivariate statistical analyses (PCA and hierarchical cluster analysis, HCA), was applied to characterize the fractions and identify discriminant features associated with antiplasmodial activity. Cytotoxicity was evaluated on AB943 human fibroblast cells using a resazurin-based assay. Additionally, an in silico molecular docking study was performed to assess the binding affinity of the highlighted compounds within the receptor pocket of Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) in complex with the invasion-inhibitory peptide R1 (PDB ID: 3SRJ). 2 Bioguided fractionation of the RE sub-extract yielded fraction F2 as the most potent antiplasmodial fraction, with an IC50 of 1.38 ± 0.48 µg/mL and a selectivity index greater than 36.2. Metabolomic profiling and multivariate statistical analyses discriminated F2 from less active fractions and highlighted its distinctive chemical signature. Three major compounds preidentified in F2 namely genistein-like (C8), 7-hydroxy-3,5 dimethylisochromen-1-one-like (C3), and eupatorin-like (C5), exhibited promising in silico binding affinities within the PfAMA1 receptor pocket, with favorable interaction profiles compared to the reference inhibitory peptide R1. This study demonstrates that integrating bioguided fractionation, untargeted metabolomics, and computational approaches is a robust strategy for accelerated identification of bioactive scaffolds from medicinal plants. The findings validate the ethnopharmacological use of Aloe rigens against malaria and highlight genistein-like, 7-hydroxy-3,5-dimethylisochromen-1-onelike, and eupatorin derivatives as promising candidates for further antimalarial drug development.
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BibTeX
@misc{elmi2026integrative,
title = {{Integrative metabolomics, molecular networking and in silico analysis reveal bioactive antiplasmodial fractions from Aloe rigens}},
author = {Abdirahman Elmi and A. Said Mohamed and Kevin Calabro and Dominique Laurain-Mattar and Fatouma M. Abdoul Latif and Philippe Grellier and Rosella Spina and abdirahman elmi fourreh},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009417/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009417/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Integrative metabolomics, molecular networking and in silico analysis reveal bioactive antiplasmodial fractions from Aloe rigens
AU - Abdirahman Elmi
AU - A. Said Mohamed
AU - Kevin Calabro
AU - Dominique Laurain-Mattar
AU - Fatouma M. Abdoul Latif
AU - Philippe Grellier
AU - Rosella Spina
AU - abdirahman elmi fourreh
PY - 2026
DA - 2026/09/24
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009417/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009417/v1
AB - Aloe rigens Reynolds & Bally (Asphodelaceae) is widely used in traditional medicine against malaria and demonstrated potent biological activity in our previous study. Despite its traditional use, its specific chemical and biological properties have not yet been comprehensively investigated. This study aimed to identify the phytochemical constituents responsible for the antiplasmodial activity of this plant through an integrated bioguided fractionation, untargeted metabolomics, and computational approach. Bioguided fractionation of Aloe rigens leaf extracts was conducted against Plasmodium falciparum (FcB-1 strain) using the SYBR Green fluorescence assay. The bioactive dichloromethane (RD) and ethyl acetate (RE) sub-extracts were profiled by LC-HRMS/MS and GC-MS. Untargeted metabolomic analysis, combining molecular networking (GNPS) with multivariate statistical analyses (PCA and hierarchical cluster analysis, HCA), was applied to characterize the fractions and identify discriminant features associated with antiplasmodial activity. Cytotoxicity was evaluated on AB943 human fibroblast cells using a resazurin-based assay. Additionally, an in silico molecular docking study was performed to assess the binding affinity of the highlighted compounds within the receptor pocket of Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) in complex with the invasion-inhibitory peptide R1 (PDB ID: 3SRJ). 2 Bioguided fractionation of the RE sub-extract yielded fraction F2 as the most potent antiplasmodial fraction, with an IC50 of 1.38 ± 0.48 µg/mL and a selectivity index greater than 36.2. Metabolomic profiling and multivariate statistical analyses discriminated F2 from less active fractions and highlighted its distinctive chemical signature. Three major compounds preidentified in F2 namely genistein-like (C8), 7-hydroxy-3,5 dimethylisochromen-1-one-like (C3), and eupatorin-like (C5), exhibited promising in silico binding affinities within the PfAMA1 receptor pocket, with favorable interaction profiles compared to the reference inhibitory peptide R1. This study demonstrates that integrating bioguided fractionation, untargeted metabolomics, and computational approaches is a robust strategy for accelerated identification of bioactive scaffolds from medicinal plants. The findings validate the ethnopharmacological use of Aloe rigens against malaria and highlight genistein-like, 7-hydroxy-3,5-dimethylisochromen-1-onelike, and eupatorin derivatives as promising candidates for further antimalarial drug development.
ER -