Neuroprotective effects of Prosopis cineraria L. ameliorate Alzheimer's disease manifestations

Prosopis cineraria is traditionally used to enhance cognitive function and manage mental disorders. Its stem bark is valued in ethnomedicine, but its potential anti-Alzheimer's disease (AD) effects are scientifically unexplored.

This research has examined the neuroprotective effects of the ethyl acetate fraction of P. cineraria bark (Pc-EA) against AlCl₃-induced AD pathology, focusing on behavioral, biochemical, histological, and molecular outcomes.

Diseased rats were treated with Pc-EA (30, 100, and 300 mg/kg) for 42 days. Cognitive and affective functions were evaluated with behavioral tests on days 29-42. Biochemical assays measured oxidative stress and cholinesterase activity, while RT-PCR quantified neuroinflammatory markers. Histopathological examination was performed to evaluate the integrity of hippocampal regions. Bioactive compounds were identified by phytochemical profiling (HPLC, GC-MS), and molecular docking was performed to assess binding interactions with acetylcholinesterase.

AlCl₃ exposure impaired memory, augmented anxiety and depression-like behavior, elevated oxidative stress, AChE activity, and induced hippocampal neurodegeneration with upregulated BACE-1, Tau, Caspase-3, and NF-κB alongside downregulated BDNF. These changes were reversed by Pc-EA (100 mg/kg), which enhanced cognitive function, restored antioxidant defense, inhibited AChE and neuroinflammatory markers, and maintained hippocampal architecture. Bioactive phytoconstituents (chlorogenic acid, kaempferol, quercetin), which exert anti-amyloidogenic, antioxidant, anti-inflammatory, and acetylcholinesterase inhibitory effects, were identified by HPLC and GC-MS, and their potential roles were corroborated via in silico validation.

Pc-EA demonstrated multi-targeted neuroprotection in AlCl₃-induced AD, which is consistent with ethnomedicinal claims. These findings indicate P. cineraria as a potential modulator of AD through antioxidant, anti-inflammatory, anti-amyloidogenic, and neurotrophic mechanisms.