Abstract

Highlight

• The environmental neurotoxicity of heavy metals and trace elements.
• The anti-inflammatory/antioxidant properties of berberine against the neurodegenerative disorders.
• Beberine as multipotent anti-Alzheimer like disorder compound.

Heavy metals are reported as neurodegenerative disorders progenitor. They play a role in the precipitation of abnormal ß-amyloid protein and hyper-phosphorylated tau, the main hallmarks of Alzheimer’s disease (AD). The present study aimed to validate the heavy metals-induced Alzheimer’s-like disease in rats as an experimental model of AD and explore the therapeutic effect of berberine via tracking its effect on the oxidative stress-inflammatory pathway. Alzheimer’s-like disease was induced in rats orally by a mixture of aluminium, cadmium and fluoride for three months, followed by berberine treatment for another one month. Berberine significantly improved the cognitive behaviors in Morris water maze test and offered a protective effect against heavy metals-induced memory impairment. Docking results showed that berberine inhibited AChE, COX-2 and TACE. Matching with in silico study, berberine downregulated the AChE expression and inhibited its activity in the brain tissues. Also, it normalized the production of TNF-a, IL-12, IL-6 and IL-1ß. Moreover, it evoked the production of antioxidant Aß40 and inhibited the formation of Aß42, responsible for the aggregations of amyloid-ß plaques. Histopathological examination confirmed the neuroprotective effect of berberine. The present data advocate the possible beneficial effect of berberine as therapeutic modality for Alzheimer’s disease via its antiinflammatory/antioxidant mechanism.

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