In silico docking and in vivo assessment of Mondia whitei fruit extract in attenuating CdCl2-Induced neurodegeneration in rat

Abstract

Cadmium is a toxic heavy metal found in the atmosphere. Its frequent exposure can lead to neurodegeneration. Medicinal plants are scavengers of free radicals that could result from exposure to heavy metals. In this study, the neuroprotective effect of the aqueous extract of <i>Mondia whitei</i> fruit (AEMW) against cadmium chloride (CdCl₂)-induced neurotoxicity was investigated using an <i>in silico</i> and <i>in vivo</i> approach. The biological constituents in the AEMW were identified using high-performance liquid chromatography, and the compounds were docked against a target protein related to neurodegeneration. Rats were exposed to CdCl₂ at 5 mg/kg for 5 days and co-treated with AEMW (250 or 500 mg/kg) for 7 days via oral administration. The levels of biogenic amines and activities of cholinergic and oxidative stress biomarkers were also evaluated. The molecular docking and ligand interactions of this study identified rutin, quercetin and kaempferol as the hit compounds with binding affinities of -15.197, -12.181 and -11.327 kcal/mol for acetylcholinesterase (AChE), and 10.325, -7.168 and -6.558 kcal/mol for human serotonin transporter (SERT), respectively. Cadmium chloride caused a significant (p < 0.05) elevation in the activities of AChE and BChE, and the levels of dopamine, serotonin and malondialdehyde with a significant (p < 0.05) decrease in the antioxidant activities. Co-administration of CdCl₂ with AEMW, especially at the dose of 500 mg/kg, attenuated the effect of CdCl₂ in the rats. Similar effect was also observed in the rat's brain histology. Therefore, AEMW could be a potential cholinesterase inhibitor to manage neuronal damage caused by heavy metal.