Author Identifier
Rasheed Abdulraheem: https://orcid.org/0000-0002-8519-8508
Date of Award
2026
Keywords
Alzheimer's disease, Beta-amyloid, Sorghum bicolor, polyphenols, complementary therapy
Document Type
Thesis
Publisher
Edith Cowan University
Degree Name
Doctor of Philosophy
School
School of Medical and Health Sciences
First Supervisor
W.M.A.D. Binosha Fernando
Second Supervisor
Prashant Bharadwaj
Third Supervisor
Ralph Martins
Fourth Supervisor
Zhaoyu Li
Fifth Supervisor
Ranil Coorey
Abstract
There is growing interest in safe, affordable, and biocompatible plant-based therapies to support individuals with Alzheimer’s disease (AD). Sorghum bicolor, the world’s fifth most important cereal grain, is rich in nutrients and bioactive compounds; however, its potential as a functional food for neuroprotection has largely been overlooked. To address this gap, this thesis undertakes a multidisciplinary investigation of sorghum polyphenol extracts, with particular emphasis on the unique 3-deoxyanthocyanidins (3-DXAs), to determine their potential to mitigate AD-related pathology.
The thesis progresses systematically from literature review to chemical characterisation, mechanistic studies, and whole-organism validation. Chapter 2 reviews current evidence linking dietary polyphenols to AD prevention and management, identifying key knowledge gaps. Chapter 3 characterises the polyphenol composition of different sorghum genotypes, providing novel phytochemical insights. Chapter 4 examines the effects of crude and purified polyphenol extracts on beta-amyloid 42 (Aβ₄₂) aggregation and neurotoxicity, integrating transcriptomic analyses to elucidate underlying molecular mechanisms. Chapter 5 focuses on 3-DXAs (apigeninidin chloride, luteolinidin chloride, and 7-methoxyapigeninidin chloride), combining molecular dynamics simulations with cell-based assays to clarify mechanisms of action. Chapter 6 validates neuroprotective effects in vivo using transgenic Caenorhabditis elegans models, assessing behavioural functions, neuronal integrity, and lifespan.
Comprehensive phytochemical profiling of black, red-brown, and red sorghum identified 29 distinct polyphenols, including five (astilbin, apigetrin, oninin, 5-O-methylgenistein, and neochlorogenic acid) reported in sorghum for the first time. Black sorghum exhibited the richest and most diverse composition. In vitro studies using MC-65 human neuroblastoma cells demonstrated that both crude and purified extracts, as well as individual 3-DXAs, exerted multitarget neuroprotective effects. These include inhibition of Aβ₄₂ aggregation, reduction of neurotoxicity, attenuation of oxidative stress, and preservation of mitochondrial function. Transcriptomic analyses further revealed downregulation of pro-inflammatory and AD related genes within the MAPK/NF-κB signalling pathway. In vivo validation in transgenic C. elegans corroborated these findings, with extracts reducing neurodegeneration, improving behavioural function, and marginally extending lifespan.
Collectively, these results provide the first comprehensive evidence that sorghum polyphenol extracts exert multitarget neuroprotective effects relevant to AD. This work expands the phytochemical understanding of sorghum, establishes its potential as an affordable functional food-based intervention, and lays a strong foundation for translational research, including bioavailability, pharmacokinetics, and future clinical trials.
Access Note
Access to this thesis is embargoed until 25th April 2029
Recommended Citation
Abdulraheem, R. A. (2026). Neuroprotective potential of Sorghum bicolor polyphenols in Alzheimer's disease: Phytochemical profiling, mechanistic insights, and preclinical validation in Caenorhabditis elegans. Edith Cowan University. https://doi.org/10.25958/bqq9-b321