EFFECT OF BITTER ASH (QUASSIA UNDULATA GUILL & DIETR.) AND AIDAN (TETRAPLEURA TETRAPTERA SCHUM & THONN) LEAF EXTRACTS ON KEY ENZYMES LINKED TO NEURODEGENERATION AND TDP-43-AMYLOID AGGREGATION.

Abstract

This study investigated a nutraceutical approach to the management of neurological disorders (ND). Aqueous extracts of aidan (Tetrapleura tetraptera) and bitter ash (Quassia undulata) were prepared, lyophilised and then pulverized. The total phenol and total flavonoid contents were determined. Also determined was the antioxidant activities in both cell free [2,2-diphenyl-1- picrylhydrazyl radical (DPPH*), 2,2- azinobis (3-ethylbenzothiazoline-6-sulfonate radical (ABTS*), Fe- chelation and ferric reducing antioxidant property (FRAP)] and cell based systems [glutathione peroxidase (GPx), glutathione reductase (GR)]. The effects of the aqueous extracts of aidan and bitter ash on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), monoamine oxidase (MAO) and beta secretase activities were determined in vitro. The tolerance/ effective safe dose of the extracts was determined. The effect of the extracts on behavioural status and key enzymes linked to neurodegeneration in scopolamine- induced brain damage in Wistar rat was investigated. Also, the effect of the extracts on amyloid peptide aggregation was determined. Phenolic constituents of the plants were characterized using high performance liquid chromatography coupled with a diode array detector (HPLC-DAD). Total phenol and flavonoid contents of aidan plant (27.14 mg/g; 18.28 mg/g) were significantly (p < 0.05) higher than bitter ash (24.76mg/g; 12.22 mg/g) plant. The aqueous extracts had antioxidant activities in vitro and in the neuronal and endothelial cells as typified by the cellular antioxidant activity; and also increased the activities of intracellular GPx and GR in both cell lines. The extracts also reduced malondialdehyde (MDA) production in both cell lines. Furthermore, the extracts inhibited AChE, BuChE, MAO and beta secretase activities in vitro. The tolerance/effective safe dose of the extracts ranged from 50- 2000 mg/kg body weight. Both extracts increased the memory index of the scopolamine induced rats. Similarly, the aqueous extracts inhibited TDP-43 amyloid aggregation in humanized yeast cells. P- coumeric acid, rutin and quercetin were revealed by HPLC-DAD as the most predominant phenolic compounds in both plant extracts. The antioxidant ability of the extracts and their inhibitory effect on some key enzymes and biomolecules linked to ND pathology is an indication of their potential as nutraceuticals/functional food in the management of ND.