Naringin mitigate okadaic acid-induced cognitive impairment in an experimental paradigm of Alzheimer's disease

• Okadaic acid (OKA) induces memory impairment in rat.
• Memory impairment was coupled with enhanced oxidative stress and inflammatory signalling.
• Naringin administration ameliorated behavioural, biochemical and molecular alterations.
• Naringin protects by downregulation of cortical and hippocampal NF-κB and downstream mediators.

Okadaic acid (OKA), a selective and potent inhibitor of serine/threonine phosphatases 1 and 2A, induces hyper-phosphorylation of tau and thus has emerged as an effective tool to develop AD like pathology in animals. In the present study, we investigated the effect of naringin, against ICV-OKA-induced cognitive impairment as assessed by Morris water maze task which was accompanied by significantly enhanced oxidative-nitrosative stress, TNF-α, TGF-β, NF-κB, caspase-3 and IL-1β levels as well as increased acetylcholinesterase and mitochondrial enzyme activities in hippocampus and cerebral cortex of rats. Treatment with naringin significantly and dose dependently improved ICV-OKA-induced cognitive deficits. The protective effects of naringin were targeted on downregulation of cortical and hippocampal cholinesterase as well as NF-κB along with downstream mediators. The protective effects of naringin (200 mg/kg) were similar to these of rivastigmine (2 mg/kg) in ICV-OKA-induced rats implicating that naringin has a potential to be explored as a novel strategy for treatment of dementias.