Pistagremic acid from Pistacia integerrima as a natural multi-target candidate tackling crucial enzymes involved in Alzheimer’s disease

Natural products have crucial relevance both in traditional medicine as well as in modern drug discovery. Indeed, they inspire currently developed drugs, emphasizing the importance of biodiversity and sustainability. Alzheimer’s disease (AD), a complex neurodegenerative disorder marked by amyloid plaques and neurofibrillary tangles, involves dysregulation of molecular pathways including increased cholinesterases and monoamine oxidase-B (MAO-B) activities, with enzyme inhibition remaining a key therapeutic strategy. This study investigates pistagremic acid, a triterpene from Pistacia chinensis subsp. integerrima and its inhibitory effects on such crucial enzymes implicated in AD. The compound showed moderate inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro with selectivity for AChE, while a potent inhibition of MAO-B was noted, indicating potential neuroprotective effects by reducing oxidative stress. Molecular docking showed interactions with key enzyme residues, and off targets were studied with a ligand-based approach. The findings support its multi-target therapeutic potential, but also prompt future studies exploring selectivity profile.