Phytochemicals from African eggplants (Solanum macrocarpon L) and Black nightshade (Solanum nigrum L) leaves as acetylcholinesterase inhibitors: an in-silico study

Acetylcholinesterase inhibitors (AChEIs) like donepezil are commonly used to treat Alzheimer's disease. AChEIs have also been considered for other therapeutic uses, such as anti-inflammatory neuroprotective agents. Consequently, the use of natural plant products as potential AChEIs can have therapeutic benefits. We previously reported the anticholinesterase properties of the phenolics and alkaloids found in the leaf extracts of two tropical plants with nutritional and ethnobotanical importance-African eggplant (Solanum macrocarpon L) and Black nightshade (Solanum nigrum L). Here, we tested the ability of both extracts to inhibit human erythrocyte AChE (an indirect mediator of pro-inflammatory cytokines production via acetylcholine degradation). We further used molecular docking and MD simulation to identify the potential molecular mechanism(s) of phenolic and alkaloid compounds as human AChEIs. Special focus was given to compounds containing the benzyl group that can establish stacking interactions similar to donepezil (a standard AChEI). Flavone-luteolin rutinosides (LR) were identified as single-binding or dual-binding AChEIs; specifically, we attributed the dual-binding LR4 and LR5 to their linked hexose moiety. This characteristic allows the dual binders to occupy the catalytic triads and the peripheral anionic subsite, while exploring the catalytic gorge. We further delineated the inhibition of human erythrocyte AChE, as the flavone common to both plant extracts-luteolin rutinosides-had positive in silico interactions with AChE. These findings suggest that phytochemicals from S. macrocarpon and S. nigrum with dual binding properties can be potential AChE inhibitors. In fact, compounds such as LR4 and LR5 should be further investigated as potential inhibitors of human AChE and may represent important natural alternatives to donepezil. Communicated by Ramaswamy H. Sarma