Arora_2024_Mol.Neurobiol__

Alzheimer's disease (AD) is a significant form of dementia. Embelin (EMB) is a natural compound with varied actions that could help prevent AD pathology. Herein, we have investigated the neuroprotective potential of EMB against Abeta(1-42)-induced neurotoxicity in rats. In this experiment, Alzheimer-like dementia was induced in rats by infusing Abeta1-42 oligomers directly into the brain's ventricles. Subsequently, the Abeta1-42-intoxicated rats received treatment with varying doses of EMB (2.5, 5, and 10 mg/kg, administered intraperitoneally) over 2 weeks. The spatial and non-spatial memory of animals was assessed at different time intervals, and various biochemical, neurochemical, and neuroinflammatory parameters in the hippocampal brain tissue of the rats were analyzed. Infusion of Abeta(1-42) in rat brain caused cognitive impairment and was accompanied by increased acetylcholinesterase activity, oxidative stress, and elevated levels of pro-inflammatory cytokines (such as TNF-alpha, IL-1beta, and IL-6) in the hippocampal tissue. Moreover, a significant decline in the levels of monoamines and an imbalance of GABA and glutamate levels were also observed. EMB treatment significantly mitigated Abeta1-42-induced cognitive deficit and other biochemical changes, including Abeta levels. The EMB-treated rats showed improved learning and consolidation of memory. EMB also attenuated Abeta-induced oxidative stress and neuroinflammation and restored the levels of monoamines and the balance between GABA and glutamate. The observed cognitive benefits following EMB treatment in Abeta(1-42)-infused rats may be attributed to its antioxidant and anti-inflammatory properties and ability to restore hippocampal neurochemistry and Abeta levels. The above findings indicate the therapeutic potential of EMB in neurodegenerative pathologies associated with cognitive decline, such as Alzheimer's disease.