Khairinisa_2025_Comput.Biol.Med_197_110970

Centella asiatica, commonly known as Gotu Kola, has been used for centuries in traditional medicine due to its neuroprotective and cognitive-enhancing properties. This study explores the potential of bioactive compounds from Centella asiatica, including asiaticoside, madecassoside, and asiatic acid, as natural inhibitors of acetylcholinesterase (AChE), a key enzyme implicated in neurodegenerative disorders such as Alzheimer's disease. Using a comprehensive in silico approach, we performed multiple-ligand mapping, docking simulations, molecular dynamics (MD) simulations, and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations. Docking results revealed that asiaticoside and madecassoside exhibited strong binding affinities to the AChE active site, with binding free energies of -190.87 kJ/mol and -197.06 kJ/mol, respectively, outperforming the reference compound Donepezil (-133.51 kJ/mol). MD simulations further confirmed the stability of these interactions, supported by consistent hydrogen bonding with key residues, including Trp86, Tyr72, Trp286, Ser293, Phe295, Tyr337, Phe338, and Tyr341. MM-PBSA calculations validated these findings, highlighting the potential of Centella asiatica compounds as effective and stable AChE inhibitors. These results underscore the promise of Centella asiatica as a natural source for developing novel therapeutics targeting cognitive decline and neurodegenerative diseases.