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

Abstract

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.

The Protective Effects of Pistacia Atlantica Gum in a Rat Model of Aluminum Chloride-Induced Alzheimer’s Disease via Affecting BDNF and NF-kB

“…Previous studies have highlighted the high antioxidant content of P. atlantica leaves, suggesting potential protection against oxidative damage (42). Extracts of P. atlantica have demonstrated potent acetylcholinesterase (AChE) inhibitory, antioxidant, and antiproliferative effects (24,26,(52)(53)(54)(55). Moreover, several articles have discussed the anti-Alzheimer effects of P. atlantica (56)(57)(58).…”

“…Moreover, several articles have discussed the anti-Alzheimer effects of P. atlantica ( 56 - 58 ). A study by Ben Ahmed et al illustrated the potential of P. atlantica galls as a source for novel anti-AD substances, identifying metabolites in P. atlantica gall extracts that may contribute to anticholinesterase activity ( 26 ). Nuzzo et alindicated that consuming pistachios with a high-fat diet prevented the negative effects of the diet on neurons and improved metabolic parameters, including oxidative stress, apoptosis, and mitochondrial dysfunction in mice ( 59 ).…”

“…Regarding the neuroprotective properties, in traditional Persian medicine, the essential oils of this species have been prescribed to promote memory ( 22 ). It has been depicted that some phenolic compounds such as methyl gallate and digalloylquinic have acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BuChE) activity, a hopeful source for finding and expanding new anti-Alzheimer agents ( 26 ). The protective effects of P. atlantica extract (150 mg/kg/day, orally) were also observed in mercury-treated rats (2.5 mg/kg, once a week, i.p.…”

Effect of Ecotype and Environment on Oil Content, Fatty Acid, and Sterol Composition of Seed, Kernel, and Epicarp of the Atlas Pistachio

“…The two main polyunsaturated fatty acids (PUFA) are linoleic acid (LA) and α-linolenic acid (ALA), precursors of the fatty acid families "ω-6 and ω-3", respectively, which are essential and specific fatty acids for health. They may play a role in reducing inflammatory diseases, such as rheumatoid arthritis, obstructive cardiovascular disease, diabetes, osteoporosis, and certain disorders such as Alzheimer's disease [3,35].…”

“…The various parts of the Atlas pistachio, including the resin, leaves, fruits and galls, have been used for a long time in diverse regions as efficient remedies for a wide range of diseases. For instance, leaves, gull, and gum resin have a wound-healing effect and have been used to treat digestive and gastrointestinal disorders, diabetes, Alzheimer, hepatic, kidney, and brain diseases [1][2][3][4]. The Atlas pistachio's fruits are also a very abundant source of bioactive compounds [5,6].…”