Protective effect of a standardized Allium jesdianum extract in an Alzheimer's disease induced rat model

Abstract

Alzheimer's disease (AD) is a complex disorder with multiple underlying mechanisms. Existing treatment options mostly address symptom management and are associated with numerous side effects. Therefore, exploring alternative therapeutic agents derived from medicinal plants, which contain various bioactive compounds with diverse pharmacological effects, holds promise for AD treatment. This study aims to assess the protective effects of the hydroalcoholic extract of Allium jesdianum on cognitive dysfunction, mitochondrial and cellular parameters, as well as genetic parameters in an intracerebroventricular Streptozotocin (icv-STZ) induced rat model of AD. Male Wistar rats were injected with a single dose of STZ (3 mg/kg, icv) to establish a sporadic AD model. A. jesdianum extract (100, 200, and 400 mg/kg/day) and donepezil (5 mg/kg/day) were orally administered for 14 days following model induction. Cognitive function was evaluated using the radial arm water maze test. Mitochondrial toxicity parameters in various brain regions (whole brain, frontal cortex, hippocampus, and cerebellum) were assessed. Gene expression analysis of miR-330, miR-132, Bax, and Bcl-2 in isolated rat brain neurons was performed using RT-qPCR. A. jesdianum extract significantly attenuated cognitive dysfunction and mitigated mitochondrial toxicity induced by icv-STZ administration. Following STZ injection, there was upregulation of Bax gene expression and downregulation of miR-330, miR-132, and Bcl-2 gene expression. Treatment with A. jesdianum extract resulted in the reversal of the expression of these microRNAs and genes, indicating its potential for improving AD and reducing neuronal apoptosis. This study demonstrates the neuroprotective capabilities of A. jesdianum against STZ-induced oxidative stress and cognitive impairment in rats, highlighting its therapeutic potential in the management of AD.

Keywords: Allium jesdianum; Alzheimer’s disease; Bax; Bcl-2; Mitochondria; Radial Arm Water Maze; microRNA (miRNA).