Integrated Network Pharmacology, In Vitro Validation, and Molecular Simulation Approaches Reveal the Neuroprotective Mechanisms of Colocasia esculenta Against Alzheimer’s Disease

Abstract

This study evaluated the antioxidant, anti-cholinesterase, and neuroprotective potential of the
ethanolic leaf extract of Colocasia esculenta using in vitro and in silico approaches against Alzheimer’s
disease (AD). The extract exhibited significant antioxidant activity in DPPH and FRAP assays with IC₅₀
values of 51.49 μg/mL and 47.55 μg/mL, respectively, along with notable acetylcholinesterase
inhibitory activity (IC₅₀ = 85.24 μg/mL). LC-MS analysis identified major bioactive compounds including
pelargonidin-3-glucoside and luteolin 7-O-glucoside. Network pharmacology revealed key AD-related
targets such as CHRM1, ACHE, GSK3B, DRD2, and GRIN1, with involvement of PI3K-Akt, calcium, TNF,
and IL-17 signaling pathways. Molecular docking demonstrated strong binding interactions of the
identified phytoconstituents with ACHE and CHRM1 proteins, while molecular dynamics simulation
confirmed the stability of the ligand-protein complexes. Overall, the findings suggest that Colocasia
esculenta possesses promising multi-target neuroprotective activity and may serve as a potential
natural candidate for Alzheimer’s disease management.