Chronic Administration of Piperine Attenuates Behavioural, Biochemical and Histological Alterations induced by Intracerebroventricular Streptozotocin in Rats.
Basic Clin Pharmacol Toxicol. 2018 Jun 11. Epub 2018 Jun 11. PMID: 29890032
Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Piperine is the major bio-active component of pepper. The aim of this study was to determine potential effects of chronic treatment with piperine on underlying biochemical, histological and behavioral changes following intracerebroventricular streptozotocin injection. Adult male Wistar rats, weighing 200-220g, were randomly assigned into 9 groups. In order to provide an animal model of the AD, streptozotocin (STZ) was bilaterally injected (3 mg/kg) into the lateral ventricles (ICV) twice on days 1 and 3. The rats were given piperine at various doses ranging from 2.5, 5, 10 and 20 mg/kg for 28 consecutive days, starting from 7 days after the second STZ injection. Morris water maze test was used to evaluate the spatial memory. One day after completion of the behavioural study, animals were decapitated and the bilateral hippocampi dissected for biochemical and histolopathological studies. Results showed that markedly spatial memory impairment is well correlated with increment of lipid peroxidation and decline in the antioxidant status and neuronal loss of the hippocampus in the STZ-injected rats. Interestingly, results showed that the cytoarchitecture of the hippocampal sub-regions retained their integrity during chronic treatment with piperine, and the behavioural test performed revealed that chronic piperine administration for 28 days showed improvements in cognitive performance and attenuated oxidative stress in the hippocampus tissue following ICV-STZ injection in a dose-dependent manner. Moreover, piperine supplementation at a physiologically relevant dose (5mg/kg/day) successfully restored antioxidant status and produced dose-dependent effects by promotion of neuronal survival rate in the hippocampus, which is comparable to that positive beneficial effects observed in donepezil (1 mg/kg/day, i.p) treated group. These findings suggest that long-term piperine supplementation improved STZ-induced cognitive impairment and enhanced the same survival rate of hippocampal neurons as in group receiving donepezil via ROS-related redox regulation and antioxidant defence mechanism potentiation in the hippocampus. This article is protected by copyright. All rights reserved.