Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 111, Issue -, Pages 432-444Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2017.11.025
Keywords
Alzheimer's disease; Heavy metals; Berberine; Amyloid-beta 40/42; Tau protein; Proinflammatory cytokines and In silico analysis
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Funding
- Science and Technology Development Fund, ministry of scientific research, Egypt [4779]
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Heavy metals are reported as neurodegenerative disorders progenitor. They play a role in the precipitation of abnormal beta-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-alpha, IL-12, IL-6 and IL-1 beta. Moreover, it evoked the production of antioxidant A beta 40 and inhibited the formation of A beta 42, responsible for the aggregations of amyloid-beta 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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