Caralluma dalzielii as a Potential Therapy for Alzheimer’s Disease: Insights from a Transgenic Drosophila melanogaster Model

This study investigated the neuroprotective potential of the methanol extract of Caralluma dalzielii (CDME) against Alzheimer’s disease (AD) using transgenic Drosophila melanogaster as a model organism. Fresh plant materials were collected, authenticated, shade-dried, and subjected to maceration extraction with 70% methanol. Phytochemical screening and High-Performance Liquid Chromatography (HPLC) analysis identified secondary metabolites in the extract. Transgenic AD model flies expressing human Aβ-42 peptide were generated and exposed to dietary supplementation with CDME at 1 mg, 10 mg, and 20 mg/10 g diet for 14 days as the case may be. Behavioral assays, including negative geotaxis, grooming, and aversive phototaxis suppression (APS), were conducted to assess locomotion, anxiety-like behavior, and memory performance. Neurobiochemical assays evaluated glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), acetylcholinesterase (AChE), and triacylglycerol (TAG) levels in fly heads. Results showed significant improvements in survival rate, locomotor activity, and learning performance at both CDME doses compared to the control (p<0.05). CDME administration led to dose-dependent increases in GSH and SOD levels, reductions in MDA and AChE activity, and enhanced TAG levels. Molecular docking analysis revealed strong binding affinities of CDME-derived compounds to glycogen synthase kinase 3 (GSK3) and β-secretase (BACE 1), key enzymes in AD pathogenesis, with several compounds outperforming the reference drug donepezil. These findings suggest that CDME possesses neuroprotective properties, potentially mitigating AD symptoms through antioxidative and cholinergic mechanisms. Further studies are recommended to isolate active compounds and explore their therapeutic potential. This study highlights the promise of Caralluma dalzielii as a natural candidate for AD management.