Pharmacological evaluation of Embelin in Benzo[α]pyrene induced experimental model of cognitive and memory impairment in mice

Abstract Alzheimer's disease (AD) is a neurodegenerative disease that affects the neurons in the hippocampus, resulting in cognitive and memory impairment. The production of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuroinflammation in neurons are the most prominent clinical characteristics of AD. It has been proven that Embelin (Emb) possess antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, we assessed the therapeutic potential of Emb in Benzo(α)pyrene (BaP)-induced cognitive impairment in experimental mice. BaP (5 mg/kg, i.p) was given to mice daily for 28 days, and Emb (2.5, 5, and 10 mg/kg, i.p) was given for 14 days after the BaP treatment. Locomotor activity was evaluated using open-field and spatial working, and non-spatial memory was evaluated using novel object recognition tasks (NORT), Morris water maze (MWM), and Y- maze. At the end of the study, the animal tissue homogenate was used to check biochemicals, neuroinflammation, and neurotransmitter changes. BaP treated mice showed a significant declined in locomotor activity, learning and memory deficits and augmented oxidative stress (lipid peroxidation, nitrite and GSH). Further, BaP promoted the release of inflammatory tissue markers, decreased acetylcholine, dopamine, GABA, serotonin and norepinephrine and increased glutamate concentration. However, treatment with embelin at dose-dependently prevented biochemical changes, improved antioxidant levels, reduced neuroinflammation, restored neurotransmitter concentration and inhibited the NF-κB pathway. The current study's finding suggested that Emb improved cognitive functions through antioxidant, anti-inflammatory, neuroprotective mechanisms and inhibition of acetylcholinesterase (AChE) enzyme activities and Aβ-42 accumulation.