Targeting Cholinesterase and Amyloid Pathology in Alzheimer’s Disease Using Plant-Derived Bioactives: A Study on Zingerone, Picroside I, And Cadambine

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, cholinergic dysfunction, and amyloid-beta (Aβ) aggregation. Despite advances in symptomatic treatments, effective disease-modifying therapies remain limited.

This study aimed to explore the neuroprotective and anti-Alzheimer potential of phytochemicals isolated from Curcuma aromatica, Picrorhiza kurroa, and Neolamarckia cadamba through phytochemical analysis, in vitro assays, and in silico molecular docking studies.

Sequential solvent extraction was followed by phytochemical screening and chromatographic isolation of bioactive compounds—zingerone, picroside I, and cadambine. Structural elucidation was performed using NMR and mass spectrometry. Molecular docking evaluated binding affinity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In vitro assays assessed cell viability, ROS scavenging, cholinesterase inhibition, and anti-amyloidogenic activity in Aβ1-42-exposed PC12 cells. ADME properties were analyzed using QikProp.

Zingerone and picroside I showed strong AChE inhibition comparable to donepezil, while cadambine demonstrated favorable ADME profiles, including high oral absorption and blood-brain barrier penetration. All compounds improved cell viability, reduced ROS levels, and inhibited Aβ aggregation, with zingerone showing the highest overall efficacy.

The findings support the therapeutic potential of these phytochemicals as multi-target agents for AD management. Zingerone and picroside I are effective enzyme inhibitors, while cadambine shows excellent drug-likeness, suggesting complementary roles in future neuroprotective drug development.