Role of arbutin and acetoside against Parkinson's disease.

abstractParkinson's disease (PD) is an incurable progressive neurodegenerative condition, which is characterized by a selective loss of dopaminergic neurons in the substantia nigra and subsequent development of motor impairment along with a non-motoric syndrome. It has a multifactorial etiopathogenesis, including oxidative stress, mitochondrial failure, lasting neuroinflammation, and α-synuclein aggregation. Interestingly, acetoside and arbutin are naturally occurring phenolic glycosides that have gained increased attention in recent times due to their strong antioxidant, anti-inflammatory, and neuroprotective capabilities. These agents have been empirically demonstrated to reduce reactive oxygen species, energize endogenous antioxidant defenses such as superoxide dismutase, catalase (CAT), glutathione, maintain mitochondrial integrity, and salvage adenosine triphosphate (ATP) generation. Furthermore, they inhibit pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), prevent the activation of caspase-3 and lipid peroxidation, regulate AMP-activated protein kinase and p62 signaling pathways, and alleviate the loss of dopaminergic neurons, which results in improved motor performance. Computational docking reports have revealed positive results between arbutin, acetoside, and key targets of PD (e.g., acetylcholinesterase [AChE], TNF-α, caspase-3, CAT, dopamine-associated proteins, and α-synuclein). Arbutin showed binding energies of - 7.6 kcal/mol (AChE), -7.0 kcal/mol (caspase-3), -9.0 kcal/mol (CAT), -8.8 kcal/mol (TNF-α), and - 7.0 kcal/mol (dopaminergic targets). In contrast, acetoside showed stronger interactions with corresponding targets, exhibiting binding energies of - 8.7 kcal/mol, -8.9 kcal/mol, -9.7 kcal/mol, and - 8.9 kcal/mol. Collectively, these findings highlight phenolic glycosides as promising multitarget neuroprotective candidates for PD.