Mohamed_2025_Iran.J.Basic.Med.Sci_28_170

OBJECTIVES: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in people over 65. The present research aimed to investigate the potential of different dietary supplements (DS) in preventing AD in an experimental animal model and in silico study. MATERIALS AND METHODS: Three DS containing a mixture of wheat-germ oil and black pepper extract/or turmeric extract were prepared. Total phenolic content, HPLC-phenolic profile, phytosterols content, fatty-acids profile, and anti-oxidant activity were evaluated in all DS. The protective effect of the prepared DS was assessed through their impact on cholinergic neurotransmission and the gene expression of GSK3beta, APP, and Akt. Oxidative stress and inflammatory markers were evaluated. The inhibition activities against acetylcholinesterase (AChE) and reduction of amyloid-beta aggregation of the major phytochemicals present in the studied DS were evaluated using in silico molecular docking study. RESULTS: Molecular docking revealed that rosmarinic acid and beta-Sitosterol exhibited the strongest binding affinities for AChE and Amyloid-beta, respectively. The results showed that all DS reduced cholinergic neurotransmission, decreased TNF-alpha as an inflammatory marker, and improved oxidative stress status. All DS down-regulated the expression of GSK3beta and APP while significantly up-regulating the expression of the Akt gene. CONCLUSION: The present study concluded that all DS enhanced cholinergic neurotransmission, reduced inflammation, and improved oxidative stress status by impacting the expression of GSK3beta, Akt, and APP genes. Rosmarinic acid and beta-sitosterol showed promising effects for treating AD, according to an in silico molecular docking study. The studied dietary supplements were considered promising candidates for the prevention of AD.