The neuroprotective effect of Xylopia parviflora against aluminum chloride-induced neurotoxicity in rats

Abstract

Neurodegenerative disease such as Alzheimer's disease, are progressive disorders which has been linked to oxidative imbalance and associated perturbations characterised by loss of memory, cognition and cholinergic deficit. To date, cholinesterase inhibition and neuroprotection are the two major strategies in drug development. Xylopia parviflora (Annonacea family) is a spice consumed in Cameroon and has been used in traditional medicine to treat various pains. In this study, X. parviflora was evaluated on behavioural studies, ion homeostasis, cholinesterase inhibitory and antioxidant activities. Rats were exposed to aluminium chloride (75 mg/kg) during 60 days, and were treated with the extract of X. parviflora (150 and 300 mg/kg BW) and two drugs references (Donepezil and Curcumin). Behavioural parameters were assessed using the Morris-Maze test and the Open Field, followed by biochemical investigations, namely, cholinesterase enzyme activity (AChE and BChE), oxidative stress (NO, MDA, GSH level, SOD and Catalase activities) and ion homeostasis (Mg²⁺ and Ca²⁺ levels). AlCl₃ administration shows a decrease in learning and memory improvement during behavioural studies, significant alteration of the central cholinergic system characterised by an increase in AChE and BChE activities to 2.72 ± 0.002 mol/min/g and 5.74 ± 0.12 mol/min/g respectively, disturbance of ion homeostasis with an increase in Ca²⁺ level (25.68 ± 3.78 μmol/mg protein) and a decrease in Mg²⁺ level (15.97 ± 2.05 μmol/mg protein) and an increase in oxidative stress compared to the positive control group. Treatment with the different doses of X. parviflora increased memory and improved locomotion, improved cholinesterase activities, ion homeostasis and stabilized brain oxidative stress levels. The study suggests that X. parviflora could potentially be used for the management of some biochemical alterations associated with Alzheimer's disease. It could even be a good alternative to chemical drugs for neurotoxicity and memory enhancement.

Keywords: Alzheimer’s disease; Antioxidant stress marker; Cholinesterase; Cognitive function; Neurotoxicity; Xylopia parviflora.

Figure 1

Effects of X. parviflora on aluminium chloride-Induced Memory Impairment in the Morris Maze Test. Animals were treated without or with AlCl₃ (75 mg/kg/BW per os), or cotreated with AlCl₃ (75 mg/kg/BW per os) and extract of Xylopia parviflora (150 and 300 mg/kg/BW/day per os) or reference compounds (Donepezil, 5 mg/kg/BW/day per os) and (Curcumin, 100 mg/kg/PC/day per os) for 60 days. Behavioural parameters (memory impairment) were performed during and at the end of the experimental (A): Effect of extract on number of entries in the target quadrant of the Morris Maze (B): Effect of extract on time spent in the target quadrant of the Morris Maze (C): Effect of extract on latency to enter in the target quadrant of the Morris Maze (D): Effect of extract on distance covered in the target quadrant of the Morris Maze. ^ap < 0.05 vs positive control (PC).

Figure 2

Effects of X. parviflora on aluminium chloride-Induced impairment in the locomotion activity in Open Field. Animals were treated without or with AlCl₃ (75 mg/kg/BW per os), or cotreated with AlCl₃ (75 mg/kg/BW per os) and extract of Xylopia parviflora (150 and 300 mg/kg/BW/day per os) or reference compounds (Donepezil, 5 mg/kg/BW/day per os) and (Curcumin, 100 mg/kg/BW/day per os) for 60 days. Behavioural parameters (locomotion impairment) were performed during and at the end of the experimental (A): Effect of extract on distance covered (B): Effect of extract on number of turnarounds; C: Effect of extract on down time. ^ap < 0.05 vs positive control (PC).

Figure 3

Microphotographs of Ammon’shorns (X400) of the hippocampus; Hematoxylin-eosin staining. Animals were treated without or with AlCl₃ (75 mg/kg/BW per os), or cotreated with AlCl₃ (75 mg/kg/BW per os) and extract of Xylopia parviflora (150 and 300 mg/kg/BW/day per os) or reference compounds (Donepezil, 5 mg/kg/BW/day per os) and (Curcumin, 100 mg/kg/BW/day per os) for 60 days. A. Normal control; B. Positive control; C. Donepezil; D. Curcumin; E. Xylopia Parviflora 150; F. Xylopia Parviflora 300.