Identification of potential anti‐Alzheimer agents from Pistacia atlantica Desf. galls using UPLC fingerprinting, chemometrics, and molecular docking analyses

The purpose of this study was to test extracts from P. atlantica Desf. galls (PAG) for anti‐acetylcholinesterase (AChE) and anti‐butyrylcholinesterase (BuChE) activity, and investigate the influence of harvesting time, plant gender, and growing location on such activity. The IC50 values of PAG extracts ranged from 56.42‐68.94 μg/ml to 82.43‐95.81 μg/ml, respectively. Our findings revealed that the anti‐AChE/BuChE activity of PAG extracts was relatively more influenced by the time of harvest than by plant gender and growing location. A combination of UPLC fingerprinting and chemometrics using partial least squares regression analysis identified the presence of two phenolic compounds, namely methyl gallate and digalloylquinic, as responsible for the anti‐AChE/BuChE activity of PAG extracts. A molecular docking study further confirmed that both compounds were able to bind to AChE and BuChE and interact with key residues of the active sites of these enzymes. Practical applications Pistacia atlantica Desf. is an important medicinal plant whose galls are traditionally used in many Mediterranean countries for the treatment of Alzheimer’s disease. The combination of fingerprint technology with chemometrical approaches in this study enabled the putative identification of metabolites in P. atlantica gall extracts responsible for anticholinesterase activity. This investigation highlights the potential of P. atlantica galls as a promising source for the discovery and development of new anti‐Alzheimer agents.