Exploring Toddalia asiatica for cognitive enhancement: Formulation, In-vitro, In-vivo, and molecular docking studies

Background: In Traditional Chinese Medicine (TCM), Toddalia asiatica (Chinese name: Fei Long Zhang Xue) is used as the principal ingredient in analgesic-hemostatic granule formulations for managing traumatic pain, bleeding wounds, and heat-associated inflammation. Although it boasts a rich phytochemical profile and traditional applications, its potential for cognitive enhancement remains largely unexplored in modern research. Objective: The cognitive-enhancing potential of Toddalia asiatica (L.) Lam was examined in this study using extraction, thin film formulation, and a combination of in-vitro, in-vivo, and in silico molecular docking methods. Methods: Extraction was carried out with ethanol, and a thin film was formulated using the ethanolic extract, which was evaluated for acetylcholinesterase (AChE) inhibition. In-vivo tests assessed the cognitive effects of both the extract and the thin film formulation. Molecular docking was performed to study the interaction of phytoconstituents with AChE. Results: Phytochemical screening confirmed the presence of several secondary metabolites. The ethanolic extract showed moderate AChE inhibition in-vitro (IC50 = 76.4 ± 3.1 μg/mL) compared to donepezil (IC50 = 4.8 ± 0.3 μg/mL). In-vivo, both the extract and its herbosomal formulation significantly and dose-dependently improved cognitive performance in treated groups compared to the illness group (p < 0.05 to p < 0.001). Molecular docking revealed favorable binding affinities of several phytoconstituents, with 8S-10-O-demethylbocconoline (TA3) showing the highest binding score (−8.66 kcal/mol) at the AChE active site. Conclusion: Toddalia asiatica demonstrates promising cognitive-enhancing activity through AChE inhibition, both in-vitro and in-vivo. These findings support its potential as a natural therapeutic candidate for managing cognitive impairments such as those seen in Alzheimer’s disease.