β‐Asarone attenuates streptozotocin‐induced experimental dementia in rats: Possible role of phosphodiesterases and cyclic nucleotide signaling

Abstract

AbstractBackgroundIn recent years, extract of Acorus calamus shown to inhibit phosphodiesterases (PDE) and β‐asarone has been reported to be a major active constituent. The purpose of the present study was to ascertain PDE inhibitory potential of β‐asarone and to explore its therapeutic potential in sporadic Alzheimer’s type dementia (SAD). In the current study, PDE inhibitory potential of β‐asarone was determined using in vitro assay system.MethodStreptozotocin (STZ) was infused intracerebroventrically [bilaterally (3 mg/kg) ICV] to induce SAD in rats. Spatial and non‐spatial memory was evaluated using Morris water maze and object recognition task in rats.Rats were treated with β‐asarone (12.5, 25 and 50 mg/kg) from day 10 to 21 following 1st STZ infusion. On day 22 rats were sacrificed and the cortical and hippocampal brain regions were used to identify biochemical alterationsResultSTZ infused rats showed significant learning and memory deficit which was linked with increase in oxidative stress (malondialdehyde and nitrite), compromised antioxidant defense (reduced glutathione), mitochondrial dysfunction (deficit in complex I and III activity) and pro‐inflammatory cytokine levels. Significant decrease in both cAMP and cGMP levels were also observed in STZ‐infused rats. β‐Asarone dose dependently attenuated STZ‐induced cognitive deficit, biochemical alterations and restored cyclic nucleotide levels.ConclusionThe observed results show important role of PDE inhibition and cyclic nucleotide signaling in the beneficial effects of β‐asarone and suggest therapeutic potential of β‐asarone in the management of cognitive disorders.