In Vivo validation of the Neuroprotective Effects of Acalypha indica leaf extract in an Aluminum Chloride-Induced Alzheimer's Disease mouse model

Abstract

Neurodegenerative disorders, particularly Alzheimer’s disease, are closely associated with cholinergic dysfunction and oxidative stress. A. indica L. is a medicinal plant traditionally used for neurological disorders and has been reported to contain phytochemicals with potential acetylcholinesterase (AChE) inhibitory activity. This study aimed to evaluate the neuroprotective effects of the ethanolic extract of A. indica in a scopolamine-induced cognitive impairment model. Thirty male Wistar rats were randomly divided into five groups (n = 6): normal control, scopolamine control, donepezil-treated, and two extract-treated groups (100 and 300 mg/kg body weight). Animals received oral treatment for 14 days, and cognitive impairment was induced by scopolamine (1 mg/kg). Spatial learning and memory were assessed using the Morris Water Maze test, followed by biochemical and histopathological analyses. Scopolamine significantly impaired cognitive performance, increasing escape latency from 21.4 ± 3.2 s to 45.8 ± 5.6 s and reducing time spent in the target quadrant from 32.6 ± 4.1 s to 14.3 ± 2.8 s (p < 0.05). Treatment with A. indica extract at 300 mg/kg significantly improved cognitive performance, reducing escape latency to 26.2 ± 3.5 s and increasing target quadrant retention time to 29.4 ± 3.9 s (p < 0.05 versus scopolamine). The extract also reduced brain AChE activity from 1.78 ± 0.19 to 1.02 ± 0.12 μmol/min/mg protein, decreased malondialdehyde levels from 3.11 ± 0.34 to 1.48 ± 0.21 nmol/mg protein, and increased superoxide dismutase activity from 4.02 ± 0.51 to 7.98 ± 0.71 U/mg protein (all p < 0.05). Histopathological examination demonstrated preservation of hippocampal neuronal architecture in extract-treated animals. The neuroprotective effects of the high-dose extract were comparable to those of donepezil. These findings indicate that the ethanolic extract of A. indica exerts significant neuroprotective effects through cholinergic modulation and antioxidant mechanisms, supporting its potential as a natural therapeutic candidate for the management of neurodegenerative disorders.