Effect of chlorogenic acid plus donepezil on critical neurocortical enzyme activities, inflammatory markers, and synaptophysin immunoreactivity in scopolamine-assaulted rats, supported by multiple ligand simultaneous docking.

Abstract

The effect of chlorogenic acid (a natural phenolic acid ubiquitous in plant foods) on selected therapeutic properties of donepezil (DON) in a scopolamine (SCOP)-induced rat model of amnesia was the focus of this study. Adult albino (Wister strain) rats were allocated into five groups (n=11) consisting of control, SCOP, SCOP + chlorogenic acid (CGA), SCOP + DON, and SCOP + CGA + DON for 7 days. Post-treatment, the rat brain cerebral cortex homogenate was assayed for cholinesterase and monoamine oxidase activities. Also, the reactive oxygen species, total thiol and nitric oxide contents, alongside catalase, and superoxide dismutase activities were determined. Routine histology for neuronal and glial cells as well as synaptophysin immunoreactivity was also carried out on the cerebral cortex. Thereafter, multiple ligand simultaneous docking was carried out for DON and CGA at the active sites of AChE and BChE. The results revealed that the biochemical parameters, glial cells, and synaptophysin immunoreactivity were significantly impaired in the cerebral cortex of scopolamine-treated rats. However, impaired butyrylcholinesterase and monoamine oxidase activity, together with antioxidant, glial cells, and synaptophysin levels were significantly ameliorated in scopolamine-treated rats administered DON + CGA compared to donepezil alone. The docking of both DON and CGA at the active sites of AChE or BChE showed higher binding energy to both enzymes compared to individual interactions of either DON or CGA. Hence, this study has been able to show that CGA could improve some of the therapeutic effects of DON, which could broaden the therapeutic spectrum of this drug. PRACTICAL APPLICATIONS: This study showed that chlorogenic acid (a major phenolic acid found in plant foods such as coffee) modulated some of the therapeutic properties of donepezil (an anticholinesterase drug used in the treatment of mild-to-moderate Alzheimer's disease). The combinations elicited better anti-butyrylcholinesterase, antimonoamine oxidase, and antioxidant properties, thus presenting this food-drug interaction as potentially able to offer better therapeutic properties.