Neuroprotective potential of sesamol and its loaded solid lipid nanoparticles in ICV-STZ-induced cognitive deficits: Behavioral and biochemical evidence

Neuroinflammation is a prominent feature of Alzheimer disease (AD) and other chronic neurodegenerative disorders. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental paradigm of Alzheimer's disease. Sesamol is a potent inhibitor of cytokine production as well as an antioxidant. The present study was designed to evaluate the effectiveness of sesamol in ICV-STZ-induced cognitive deficits in rats by incorporating it into solid lipid nanoparticles (SLNs). ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced nitrodative stress, altered acetylcholinesterase in rat brain along with significantly increased serum TNF-alpha levels. Chronic treatment with sesamol and sesamol loaded SLNs dose dependently restored cognitive deficits in ICV-STZ rats along with mitigation of nitrodative stress and cytokine release. Effectiveness of SLNs to deliver sesamol to the brain was shown by a significantly better alleviation of the oxidative stress parameters. Our findings demonstrate that loading of sesamol in SLNs is an effective strategy to mitigate ICV-STZ-induced neuronal dysfunction and memory deficits. (C) 2014 Elsevier B.V. All rights reserved.