In Silico Screening of Bioactive Phytochemicals from Centella asiatica (L.) Urb. as Human Acetylcholine Esterase Inhibitors for Cognitive Enhancement.
DOI:
https://doi.org/10.70066/jahm.v14i9.2899Keywords:
ADMET analysis, Centella Asiatica, Human acetylcholine esterase, Molecular docking, Phytochemicals.Abstract
Background: Dementia is a neurodegenerative disease characterized by progressive impairment of cognitive abilities and has become a significant global health concern. One approach is to focus on inhibiting acetylcholinesterase. Phytochemicals from Centella asiatica (L.) Urb. have been associated with cognitive enhancement and neuroprotection. In the present study, in silico docking of phytochemicals against human acetylcholinesterase (AChE) was performed to identify the phytochemical with the best binding to the catalytic site. Materials and methods: Bioactive phytochemicals associated with Centella asiatica (L.) Urb. were identified using IMMPAT, and their structures were retrieved from PubChem. These were used as lignads. The crystal structure of AChE obtained from the PDB was used as the receptor/protein for docking. AutoDock Vina and PyRx were used for docking. Two-dimensional (2D) and three-dimensional (3D) structures, and the interaction between the ligand and the protein, were evaluated using Discovery Studio and LigPlot+ analysis. ADMET properties were also analysed for the ligands. Results: Among the four phytochemicals docked against human acetylcholinesterase, asiaticoside showed the highest negative binding energy (-9.3 Kcal/mol), followed by Asiatic acid (-8.8 Kcal/mol), madecassic acid (-8.3 Kcal/mol), madecassoside (-8.2 Kcal/mol), and standard donepezil (-7.5 kcal/mol). Molecular docking revealed favorable binding of the ligands to AChE through hydrogen-bonding and hydrophobic interactions, indicating their potential to interact with the enzyme. Drug-likeness properties indicate that Asiatic acid and madecassic acid pass Lipinski's Rule of Five, while asiaticoside and madecassoside failed due to their bulky structure. ADME analysis indicated good properties, suggesting their acceptance as computationally prioritized candidates. Conclusion: Asiatic acid demonstrated favorable drug-likeness and ADME properties, despite asiaticoside showing a high docking score with AChE. This indicates that phytochemicals from Centella asiatica (L.) Urb. have potential as drug candidates for AChE inhibition. However, further in vitro and in vivo studies are needed to validate its efficacy and safety.
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