Computer-Aided Identification of Cholinergic and Monoaminergic Inhibitory Flavonoids from Hibiscus sabdariffa L

The reduced levels of acetylcholine and dopamine lead to Alzheimer's disease (AD) and Parkinson's disease PD, respectively, due to the action of cholinesterase and monoamine oxidase B.

Therapeutic options for AD and PD involve respective cholinergic and monoaminergic inhibitors, and considering the adverse outcomes of cholinergic- and monoaminergic- inhibitory therapeutics, phytoconstituents may be promising alternatives. Reports have shown that different extracts of the calyx of Hibiscus sabdariffa exhibit anticholinesterase and monoamine oxidase B inhibitory properties with the potential to delay and prevent the development of AD and PD. However, there is limited knowledge on the multitarget cholinergic and monoaminergic inhibitory activities of individual compounds in this plant. Computational methods were used to identify the specific compounds responsible for the observed cholinergic and monoaminergic inhibitory activities of the H. sabdariffa calyx extracts.

Results confirm that three flavonoids: delphinidin-3-sambubioside, kaempferol-3-O-rutinoside and quercetin-3-rutinoside showed strong binding affinity with acetylcholinesterase, butyrylcholinesterase and monoamine oxidase B while the observed stability of the ligands-enzymes complexes over the MD simulation time suggests their cholinergic and monoaminergic inhibitory properties.

The three flavonoids may be responsible for the reported anticholinergic and monoaminergic inhibitory potentials of H. sabdariffa extracts and could be enlisted as multi-target inhibitory agents for cholinesterases and monoamine oxidase B.