Evaluation of In Vitro and In Silico Anti-Alzheimer Potential of Nonpolar Extracts and Essential Oil from Mentha piperita

The anticholinesterase and antioxidant activities with chemical composition and molecular docking of essential oil and nonpolar extracts of were evaluated using enzymatic and chemical methods. Molecular docking tools were used to explain the interaction of the major chemical constituents with the enzymes. GC/MS analyses revealed that the main compounds in essential oil were l-menthone (43.601%) followed by pulegone (21.610%), linolenic acid (25.628%), and l-menthone (10.957%), representing the major compounds of the petroleum ether extract. Imidazoquinoline (7.767%) and 17-N-acetyl-oroidine (5.363%) were the major constituents of the chloroform extract. Linolenic acid (19.397%) and l-menthone (6.336%) were the most abundant compounds in the hexane extract. The essential oil and nonpolar extracts showed moderate antioxidant activity. The essential oil showed the most promising anticholinesterase activity with IC = 10.66 ± 0.12 µg/mL and IC = 16.33 ± 0.03 µg/mL against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively, close to galantamine in AChE and more active in BChE, followed by the interesting activity in the petroleum ether extract with IC = 23.42 ± 3.06 µg/mL in AChE and IC = 62.00 ± 3.22 µg/mL in BChE. The docking experiments showed that among the seven major identified compounds, N-acetyl-17-oroidine showed the highest binding score (63.01 in AChE and 63.68 in BChE). This compound was found to bind the catalytic and peripheral sites, resulting in more potent inhibitory activity than galantamine, which only binds to the catalytic site. These findings suggested the possible use of essential oil and nonpolar extracts as a potential source of alternative natural anti-Alzheimer compounds.