Therapeutic potential of Moringa oleifera phytochemicals as modulators of cathepsin B for Alzheimer’s disease management: insights from molecular docking and dynamics simulations

Abstract Background Alzheimer’s disease (AD) presents a significant challenge in healthcare due to its progressive neurodegenerative nature. Current treatments are limited, prompting the search for novel therapeutic strategies. Phytochemicals from medicinal plants offer potential neuroprotective effects, targeting various pathways implicated in AD pathogenesis. Moringa oleifera , known for its diverse health benefits, presents a promising source of phytochemicals with therapeutic potential against AD. This study aimed to investigate the neuroprotective properties of M. oleifera phytochemicals, particularly their interactions with cathepsin B, a novel target in AD pathology. Results Phytochemical analysis of M. oleifera seed extract revealed the presence of bioactive compounds, including catechin, naringenin, and ellagic acid, among others. Molecular docking simulations identified moringyne and ellagic acid as top candidates for interacting with cathepsin B, showing favorable binding affinities compared to a standard drug (Z-FA.FMK). Furthermore, ADMET prediction indicated favorable pharmacokinetic properties for moringyne and ellagic acid, suggesting their suitability as oral drugs. Molecular dynamics simulations confirmed stable interactions between the identified compounds and cathepsin B over 250 ns, with ellagic acid exhibiting superior stability. MM/GBSA analysis ranked ellagic acid as the most potent inhibitor of cathepsin B, supporting its potential therapeutic efficacy. Conclusion This study demonstrates the potential of M. oleifera phytochemicals, particularly moringyne and ellagic acid, as novel therapeutic agents against AD through their interaction with cathepsin B. These findings further demonstrate the importance of natural compounds in drug discovery and development for neurodegenerative diseases. Further preclinical and clinical studies are warranted to validate the efficacy and safety of moringyne and ellagic acid in AD treatment.