摘要：

Pregnane x receptors (PXRs) regulate the expression of ATP-binding cassette proteins transporters and organic anion transporting polypeptides responsible for influx/efflux of xenobiotics across brain. Ligand activation of PXR augments the expression of P-gp and promotes Aβ clearance across the blood brain barrier. Dementia was induced in mice by intacerebroventricular administration of streptozotocin (STZ), followed by treatment with meclizine, a PXR agonist and subsequently exposed to Morris water maze test and biochemical analysis to evaluate the effect on cognition. STZ-treated mice exhibited significant enhancement in brain thiobarbituric acid reactive species, interleukin-1β, tumour necrosis factor-α, myeloperoxidase and acetylcholinestrase activity in addition to diminution in glutathione levels and superoxide dismutase activity in comparison to untreated mice. Administration of meclizine to STZ mice recuperated cognition and biochemical alterations. Concomitant administration of ketoconazole, a PXR antagonist with meclizine prevented the protective effects. The upshots of our study proclaim that meclizine protects cognitive deficits by virtue of its antioxidant, anti-cholinesterase and anti-inflammatory properties. Results also signify the potential of PXR in neuroprotective actions of meclizine in dementia.

展开