In Vitro and In Silico Evaluation of Turmeric Extracts for Anticholinesterase Effects and their Topical Formulation for Future Application in Alzheimer’s Disease

Abstract

Purpose

Alzheimer’s disease (AD) is prevalent among older adults due to reduced acetylcholine levels and increased oxidative stress. Oral treatments cause severe side effects, promoting topical patches as alternatives. This study evaluated turmeric extracts for anti-acetylcholinesterase (AChE) and antioxidative activities, and developed a topical delivery system.

Methods

Crude ethanolic (EF), curcuminoids-rich (CRF), and alkaloid-rich fractions (ARF) were extracted from turmeric and evaluated for in vitro AChE inhibitory and in vitro antioxidant activities. Molecular docking explored curcuminoid-AChE interactions. CRF was formulated into emulsions and topical polysaccharide gel patches, then evaluated for physicochemical properties and in vitro release.

Results

CRF demonstrated highest in vitro AChE inhibitory effects (IC₅₀: 18.49 ± 1.36 µg/mL), comparable to galantamine (IC₅₀: 13.62 ± 9.22 µg/mL), and significant in vitro antioxidant activity (DPPH IC₅₀: 45.6 ± 2.61 µg/mL). Molecular docking showed strong binding affinities for curcumin, bis-desmethoxy curcumin, and desmethoxy curcumin with binding energies of − 9.91 to − 10.51 kcal/mol. Optimal CRF solubility occurred in olive oil: PEG: water (1:19:30 v/v). CRF emulsion-loaded patches achieved 41.63% AChE inhibition versus 16.65% for non-emulsified patches.

Conclusions

CRF-containing topical patches demonstrate promising therapeutic potential for AD treatment, offering a cost-effective, biocompatible alternative with enhanced bioavailability through emulsion formulation.