Publication

Abstract : Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, the accumulation of amyloid-beta (Aβ) plaques, oxidative stress, and neuroinflammation. Current therapies largely provide symptomatic relief without effectively altering disease progression, highlighting the urgent need for novel, disease-modifying strategies. Natural compounds have gained increasing attention for their ability to target multiple pathological mechanisms associated with AD. In the present study, phytochemicals derived from Elettaria cardamomum were investigated through a combination of computational and in vitro approaches. Among the screened compounds, methyl eugenol (ME), a naturally occurring bioactive molecule, emerged as a promising hit. Further molecular docking and dynamic simulations revealed that ME interacts favorably with monoamine oxidase (MAO-B), an enzyme implicated in AD pathogenesis through its role in promoting oxidative stress and neuroinflammation. The multitarget potential of ME was further confirmed through in vitro enzyme inhibition assays, demonstrating not only effective inhibition of MAO-B but also a moderate inhibitory activity against acetylcholinesterase. Moreover, ME exhibited promising neuroprotective effects in SH-SY5Y neuroblastoma cells incubated with Aβ, lipopolysaccharide, and glutamate, indicating its ability to attenuate excitotoxicity, oxidative injury, and inflammatory responses. Collectively, these findings underscore the therapeutic potential of ME as a multitarget-directed agent in AD and highlight the broader promise of phytochemicals in the development of novel interventions for neurodegenerative disorders. Significance Statement This study identifies ME as a promising multitarget agent for AD. Combining computational and in vitro approaches, ME demonstrated MAO-B and acetylcholinesterase inhibition, along with neuroprotection against Aβ, lipopolysaccharide-, and glutamate-induced toxicity. These findings support its potential to modulate key pathological features of AD and highlight the therapeutic relevance of phytochemicals in neurodegenerative drug discovery.