| Summary: | Type 2 diabetes (T2D) is associated with accelerated cognitive decline. To date, there is no T2D-specific treatment to prevent or ameliorate cognitive dysfunction. Boswellia serrate (BS) gum has been shown to possess multiple pharmacological actions including anti-inflammatory, anticancer and ant- apoptotic actions. The present study was aimed to investigate the effect of BS on cognitive impairment associated with T2D induced in rats by high fat/high fructose (HF/HFr) diet with a single injection of streptozotocin (STZ) and to explore the mechanism of action. The effect of 3 doses of BS extract and the reference drug on the behavioral, biochemical, histopathological and glutamate gene expression abnormalities in T2D rates was evaluated. HF/HFr diet/ STZ induces learning and memory deficits, which were reversed by BS extract. It showed a significant decrease in Aβ deposits and p-tau positive cells. BS extract also reduced significantly the hippocampal elevated levels of caspase-3, cholinesterase (ChE), GSK-3β, TNF-α, IL-1β, IL-6, and MDA. Moreover, BS extract enhanced significantly the suppressed hippocampal level of GSH, SOD and glutamate receptor expression (GluR, NR1, NR2 A, and NR2B). In addition, BS extract alleviated insulin resistance and hyperlipidemia of T2D rats. Our findings suggest that BS extract reversed learning and memory impairment in HF/ HFr diet / STZ induced diabetic rats. This effect may be attributed to the inhibition of insulin resistance, pro-inflammatory cytokines, oxidative stress and hyperlipidemia
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