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Purpose <p>This study aims to profile the primary and secondary metabolites of <i>Atriplex leucoclada</i> Boiss., a halophytic shrub renowned for its critical role in soil stabilization, salinity tolerance, and sustainable livestock feed. Given its significant biological activities, including anti-inflammatory and antioxidant properties, the research seeks to evaluate its potential application in combating neurodegenerative disorders, particularly Alzheimer’s.</p> Methods <p>Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight High-Resolution Mass Spectrometry (UPLC-qTOF-HRMS/MS) was employed for metabolite identification, utilizing the phytochemical-focused RIKEN tandem mass spectral database (ReSpect) and comparison with authentic standards. Biological evaluation involved assessing butyrylcholinesterase inhibition activity using an ELISA assay, followed by molecular docking studies of the identified secondary metabolites against acetylcholinesterase and butyrylcholinesterase. Using in silico ADMET analysis, the pharmacokinetic characteristics of the four chosen BChE selective bioactive inhibitor substances were assessed, with an emphasis on absorption, distribution, metabolism, and excretion (ADME) features.</p> Results <p>The tentative identification of 40 metabolites Also, the study demonstrated the effectiveness of the different fractions of <i>A. leucoclada</i> Boiss. in inhibiting the butyrylcholinesterase enzyme, which is a key contributor to the progression of Alzheimer’s disease. At a concentration of 0.364 ± 0.055&#xa0;mg/mL, the ethyl acetate fraction showed the highest efficiency, inhibiting butyrylcholinesterase by 50% (IC<sub>50</sub>). Based on the in vitro results, a molecular docking study suggested the selectivity of the tentatively identified compounds towards butyrylcholinesterase and acetylcholinesterase, as pelargonidin-3,5-<i>O</i>-di-<i>β</i>-glucopyranoside achieved the highest inhibition activity and selectivity. Procyanidin B2’s moderate clearance, metabolic stability, and comparatively high absorption make it seem like the most viable option.</p> Conclusion <p>This study highlights the potential biological significance of the tentatively identified secondary metabolites of <i>Atriplex leucoclada</i> in the context of neurodegenerative disorders, particularly Alzheimer’s disease. Furthermore, the identified primary metabolites underscore the plant’s value as a nutritional resource.</p> Graphical Abstract <p></p>

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Metabolite Profiling of Atriplex leucoclada Boiss.: Exploring its In-Vitro and In-Silico Cholinesterase Inhibition Potential by Molecular Modeling and ADMET Analysis

  • 期刊论文

  • 发表日期：

    2025年5月9日

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  • Sarah A. Badawy,
  • Ahmed R. Hassan,
  • Amany M. Korkor,
  • Marwa S. Abu Bakr,
  • Abd El-Salam I. Mohammed

摘要

Purpose

This study aims to profile the primary and secondary metabolites of Atriplex leucoclada Boiss., a halophytic shrub renowned for its critical role in soil stabilization, salinity tolerance, and sustainable livestock feed. Given its significant biological activities, including anti-inflammatory and antioxidant properties, the research seeks to evaluate its potential application in combating neurodegenerative disorders, particularly Alzheimer’s.

Methods

Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight High-Resolution Mass Spectrometry (UPLC-qTOF-HRMS/MS) was employed for metabolite identification, utilizing the phytochemical-focused RIKEN tandem mass spectral database (ReSpect) and comparison with authentic standards. Biological evaluation involved assessing butyrylcholinesterase inhibition activity using an ELISA assay, followed by molecular docking studies of the identified secondary metabolites against acetylcholinesterase and butyrylcholinesterase. Using in silico ADMET analysis, the pharmacokinetic characteristics of the four chosen BChE selective bioactive inhibitor substances were assessed, with an emphasis on absorption, distribution, metabolism, and excretion (ADME) features.

Results

The tentative identification of 40 metabolites Also, the study demonstrated the effectiveness of the different fractions of A. leucoclada Boiss. in inhibiting the butyrylcholinesterase enzyme, which is a key contributor to the progression of Alzheimer’s disease. At a concentration of 0.364 ± 0.055 mg/mL, the ethyl acetate fraction showed the highest efficiency, inhibiting butyrylcholinesterase by 50% (IC50). Based on the in vitro results, a molecular docking study suggested the selectivity of the tentatively identified compounds towards butyrylcholinesterase and acetylcholinesterase, as pelargonidin-3,5-O-di-β-glucopyranoside achieved the highest inhibition activity and selectivity. Procyanidin B2’s moderate clearance, metabolic stability, and comparatively high absorption make it seem like the most viable option.

Conclusion

This study highlights the potential biological significance of the tentatively identified secondary metabolites of Atriplex leucoclada in the context of neurodegenerative disorders, particularly Alzheimer’s disease. Furthermore, the identified primary metabolites underscore the plant’s value as a nutritional resource.

Graphical Abstract