Phenolic Profiling and Inhibitory Activities of Cholinesterase and β-Amyloid Aggregation in Ziziphus Species Fruit Fractions

In recent years, there has been growing interest in the potential of medicinal plants for preventing and treating neurodegenerative diseases. This study investigated the neuroprotective properties of aqueous extracts derived from the pulp, seed, and almonds of Ziziphus spina-christi (L.) Desf. and Ziziphus lotus (L.) Lam. These extracts were assessed in vitro for their impact on acetylcholinesterase, butyrylcholinesterase, and β-amyloid aggregation, all key factors associated with neurodegenerative disorders (NDs). Given the strong connection between NDs and oxidative damage, as well as the role of metal accumulation in exacerbating oxidative stress and amyloid plaque formation, the antioxidant abilities of the extracts were also evaluated using various methods including ferric-reducing antioxidant power, cupric-reducing antioxidant capacity, and metal chelating assays. Furthermore, the study analyzed the total phenolic and flavonoid contents using standard spectrophotometric techniques, and the secondary metabolite composition was examined through UHPLC-DAD analysis. To better understand the relationship between different plant species and their organ types with specific phenolic compounds and biological activities, principal component analysis (PCA) was employed for data analysis. Results revealed the presence of 25 secondary metabolites categorized into phenolic and flavonoid compounds. Interestingly, the seed extracts exhibited the highest bioactivity, significantly inhibiting antioxidant and cholinergic enzymes. In addition, almond extracts displayed promising antiamyloidogenic properties, effectively suppressing oligomers, fibrillation of Aβ42, and the amyloid cascade. In conclusion, this study highlights the potential of seed and almond extracts from Z. spina-christi (L.) Desf. and Z. lotus (L.) Lam. as valuable sources of natural compounds with neuroprotective properties against neurodegenerative diseases.