Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity

Alzheimer's disease (AD) significantly impacts individuals, families, and global healthcare systems, characterised by cognitive decline, memory impairment, and oxidative stress. This study investigated the potential of phytochemicals as therapeutic agents for Alzheimer's disease (AD) throu...

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Main Author: Aljadaan, Adel
Format: Thesis (University of Nottingham only)
Language:English
Published: 2025
Subjects:
Online Access:https://eprints.nottingham.ac.uk/80907/
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author Aljadaan, Adel
author_facet Aljadaan, Adel
author_sort Aljadaan, Adel
building Nottingham Research Data Repository
collection Online Access
description Alzheimer's disease (AD) significantly impacts individuals, families, and global healthcare systems, characterised by cognitive decline, memory impairment, and oxidative stress. This study investigated the potential of phytochemicals as therapeutic agents for Alzheimer's disease (AD) through an integrated approach that combines in silico and in vitro methodologies. Docking studies indicated that rutin exhibited the strongest binding affinity for acetylcholinesterase (AChE) at -14.81 kcal/mol, whereas silibinin demonstrated the highest affinity for butyrylcholinesterase (BuChE) at -9.55 kcal/mol. In vitro, assays identified berberine as the most potent AChE inhibitor, with an IC50 value of 60.99 µM, and silibinin as the most effective BuChE inhibitor, with an IC50 value of 48.95 µM. Antioxidant assessments revealed that chlorogenic acid displayed the most significant DPPH scavenging activity, with an EC50 of 126.1 µM, while silymarin was most effective in inhibiting lipid peroxidation, yielding an EC50 of 35.6 µM. Cytotoxicity evaluations indicated that berberine and quercetin-3-β-glucoside exhibited minimal toxic effects, consistent with in silico predictions, whereas rutin resulted in elevated reactive oxygen species (ROS) generation. Ex vivo analyses demonstrated a significant reduction in superoxide dismutase 1 (SOD1) levels and increased protein carbonylation in AD samples, suggesting their potential role as markers of oxidative stress. These findings highlight the potential of phytochemicals as multifunctional therapeutic agents for Alzheimer's disease (AD), demonstrating promising efficacy and low toxicity.
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spelling nottingham-809072025-07-23T04:40:14Z https://eprints.nottingham.ac.uk/80907/ Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity Aljadaan, Adel Alzheimer's disease (AD) significantly impacts individuals, families, and global healthcare systems, characterised by cognitive decline, memory impairment, and oxidative stress. This study investigated the potential of phytochemicals as therapeutic agents for Alzheimer's disease (AD) through an integrated approach that combines in silico and in vitro methodologies. Docking studies indicated that rutin exhibited the strongest binding affinity for acetylcholinesterase (AChE) at -14.81 kcal/mol, whereas silibinin demonstrated the highest affinity for butyrylcholinesterase (BuChE) at -9.55 kcal/mol. In vitro, assays identified berberine as the most potent AChE inhibitor, with an IC50 value of 60.99 µM, and silibinin as the most effective BuChE inhibitor, with an IC50 value of 48.95 µM. Antioxidant assessments revealed that chlorogenic acid displayed the most significant DPPH scavenging activity, with an EC50 of 126.1 µM, while silymarin was most effective in inhibiting lipid peroxidation, yielding an EC50 of 35.6 µM. Cytotoxicity evaluations indicated that berberine and quercetin-3-β-glucoside exhibited minimal toxic effects, consistent with in silico predictions, whereas rutin resulted in elevated reactive oxygen species (ROS) generation. Ex vivo analyses demonstrated a significant reduction in superoxide dismutase 1 (SOD1) levels and increased protein carbonylation in AD samples, suggesting their potential role as markers of oxidative stress. These findings highlight the potential of phytochemicals as multifunctional therapeutic agents for Alzheimer's disease (AD), demonstrating promising efficacy and low toxicity. 2025-07-23 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/80907/1/Thiese%2020072493.pdf Aljadaan, Adel (2025) Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity. PhD thesis, University of Nottingham. Alzheimer's disease Therapeutic agents Phytochemicals Oxidative stress
spellingShingle Alzheimer's disease
Therapeutic agents
Phytochemicals
Oxidative stress
Aljadaan, Adel
Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity
title Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity
title_full Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity
title_fullStr Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity
title_full_unstemmed Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity
title_short Potential of phytochemicals as a treatment for Alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity
title_sort potential of phytochemicals as a treatment for alzheimer’s disease: evaluation of anticholinesterase activity, antioxidant properties, and cytotoxicity
topic Alzheimer's disease
Therapeutic agents
Phytochemicals
Oxidative stress
url https://eprints.nottingham.ac.uk/80907/