Ameliorative effects of bromelain on aluminum-induced Alzheimer's disease in rats through modulation of TXNIP pathway

Alzheimer's disease (AD) is known as "type 3 diabetes". As thioredoxin binding protein (TXNIP) has been shown to be involved in brain insulin resistance, the present study evaluated the roles of TXNIP, phospho-insulin receptor substrate 1 (P-IRS-1), and phosphatidyl inositol-3 kinase (PI3K) in the pathogenesis of AD. The potential ameliorative effect of bromelain compared to donepezil was evaluated in an aluminum chloride (AlCl3)-induced AD in rats. Behavioral tests demonstrated similar improvements in exploratory activity, cognitive and spatial memory functions, anxiety, and depression levels between rats treated with bromelain and donepezil. Donepezil was superior to bromelain in improving locomotor activity. Histopathological examinations demonstrated neuronal degeneration in the AlCl3 group that was almost normalized by bromelain and donepezil. Moreover, there was deposition of amyloid plaques in the AlCl3 group that was improved by bromelain and donepezil. Acetylcholine esterase levels were significantly increased in rats treated with AlCl3 group and significantly decreased in rats treated with bromelain and donepezil. Furthermore, AlCl3 group showed a significantly increased TXNIP and P-IRS1 and a significantly reduced PI3K levels. These effects were ameliorated by bromelain and donepezil treatment. The present study demonstrates a previously unreported modulatory effect of bromelain on the TXNIP/P-IRS-1/PI3K axis in AD model.