Abstract / Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying therapies, necessitating the exploration of novel therapeutic agents. Caralluma dalzielii, a medicinal plant traditionally used for neurological disorders, has not previously been evaluated in an experimental model of AD. This study investigated the neuroprotective potential of the methanol extract of C. dalzielii (CDME) and explored its possible mechanisms of action using a transgenic Drosophila melanogaster model of AD. Transgenic flies expressing human amyloid-β42 were treated with CDME for 14 days. Behavioural performance, oxidative stress biomarkers, acetylcholinesterase levels, triacylglycerol levels, and Tau gene expression were evaluated. Molecular docking was performed to explore interactions between major phytochemicals and glycogen synthase kinase-3 (GSK3) and β-secretase (BACE1). Data were analysed using one-way analysis of variance with Dunnett’s post hoc test, with statistical significance set at p < 0.05. CDME improved survival, locomotor performance, grooming behaviour, and learning ability in AD flies. Treatment was associated with increased glutathione and superoxide dismutase levels and reduced lipid peroxidation, together with reductions in acetylcholinesterase levels and Tau gene expression. Molecular docking suggested favourable interactions between several phytochemicals and GSK3 and BACE1, with catechin showing notable predicted binding. CDME demonstrated preliminary neuroprotective effects in the transgenic Drosophila model of AD. The behavioural, biochemical, molecular, and computational findings support further investigation of C. dalzielii as a potential source of bioactive compounds for AD drug discovery. However, direct target validation, assessment of amyloid-β and Tau pathology, and studies in mammalian models are required to establish its therapeutic relevance. Caralluma dalzielii extract (CDME) improved memory and motor function in AD fly models. CDME was associated with favourable changes in antioxidant-related biochemical parameters. Acetylcholinesterase levels were significantly reduced by CDME treatment. CDME downregulates dTau gene expression. Catechin showed the most favourable docking scores against GSK3 and BACE1.