piperine and Memory-Disorders

We still do not have effective treatment for hippocampal demyelination and memory deficit, the two common comorbidities in multiple sclerosis (MS). This study aimed to assess the therapeutic effect of Piperine (the main alkaloid of black pepper) in an experimental model of demyelination.. Demyelination was induced in male Wistar rats by bilateral injection of lysolecithin (LPC) into the CA1 region of the hippocampus. Piperine (5, 10, 20 mg/kg) was daily injected intraperitoneally three days post LPC injection for ten days. The spatial memory was examined by the Morris water maze task. Demyelination and astrocyte activation were assessed by an immunohistological study. The gene expression analysis of TNF-α, IL1-β, NF-κB, IL-10, Foxp3, iNOS, Nrf2, HO1, MBP, and BDNF was done using qPCR. The total antioxidant capacity of hippocampal tissue was measured using FRAP assay.. Our results showed that piperine improved the memory performance and myelin repair in the hippocampal demyelination model. Piperine inhibited iNOS expression concomitant with enhanced expression levels of Nrf2, HO1 and the total antioxidant capacity in the hippocampal tissue. Piperine treatment significantly reduced the gene expression level of TNF-α, IL1-β, NF-κB, and glial activation in the injured area; however, the mRNA level of IL-10, Foxp3, BDNF and MBP were significantly increased.. We found piperine to be an effective treatment for spatial memory impairment and myelin repair in the hippocampal demyelination model. However, further experimental evidence is needed to investigate the precise mechanisms underlying piperine as a promising therapeutic target in MS patients.

Topics: Alkaloids; Animals; Antioxidants; Benzodioxoles; Cytokines; Demyelinating Diseases; Gene Expression Regulation; Hippocampus; Lysophosphatidylcholines; Male; Maze Learning; Memory Disorders; Models, Animal; Myelin Sheath; Neuroprotective Agents; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar; Spatial Memory

In recent years, piperine has attracted much attention due to its various biological effects as a neuroprotective agent. Therefore, clarification of the possible side effects of piperine is important to identify its potential pharmacological action. Thus, the effects of piperine on the long-term plasticity of perforant pathway to dentate gyrus synapses were studied in hippocampus of an animal model of Alzheimer's disease (AD). Adult male rats were injected with intracerebroventricular (ICV) streptozotocin (STZ) bilaterally, on days 1 and 3 (3 mg/kg). The STZ-injected rats were treated with different doses of piperine for 4 weeks before being used in behavioral, electrophysiological and histopathological experiments. The passive-avoidance test was conducted on all animals in order to determine the cognitive performance. Rats were placed in a stereotaxic frame to implant a recording electrode in the hippocampal dentate gyrus and a stimulating electrode in the perforant path. Additionally, we assessed the density of survived neurons stained by cresyl violet. In this study, chronic administration of piperine low dose improved the ICV-STZ induced learning and long-term potentiation (LTP) impairments with no significant effect on baseline synaptic activity. In contrast, remarkable learning and long-term plasticity impairments were observed in rats treated by high dose of piperine in comparison to the other groups. Interestingly, this impaired hippocampal LTP was accompanied by an obvious alteration in baseline activity and significantly decreased neuronal numbers within the hippocampus. Therefore, our data provides a new understanding of the piperine supplementation effects on hippocampal electrophysiological profile although the consequences may be either beneficial or detrimental.

Topics: Alkaloids; Animals; Behavior, Animal; Benzodioxoles; Disease Models, Animal; Hippocampus; Long-Term Potentiation; Male; Memory; Memory Disorders; Neuronal Plasticity; Neuroprotective Agents; Neurotoxicity Syndromes; Piperidines; Polyunsaturated Alkamides; Rats, Wistar; Streptozocin; Time Factors

Piperine, the major alkaloid constituent of black pepper, has been reported to possess a wide range of pharmacological effects on the central nervous system, including antidepressant, anticonvulsant and anti-ischemic activities. In the present study, we aimed to investigate the therapeutic potential and neuroprotective mechanisms of piperine in an experimental mouse model of sporadic Alzheimer's disease (sAD) induced by intracerebroventricular (ICV) infusion of streptozotocin (STZ). STZ was infused bilaterally at a dose of 1.5 mg/kg/day on day 1 and day 3. From day 8, piperine (2.5-10 mg/kg body weight) was administered intraperitoneally once daily for 15 consecutive days. The locomotor activity and cognitive performance of mice were evaluated using open field test and Morris water maze test, respectively. On day 23, all animals were sacrificed, and the hippocampus was used for biochemical, neurochemical and neuroinflammatory determinations. Our data revealed that the ICV-STZ-infused sAD mouse showed an increased oxidative-nitrosative stress, an altered neurotransmission and an elevated neuroinflammation in hippocampus, as well as significant cognitive deficits. All these alterations can be ameliorated by piperine in a dose-dependent manner. In summary, our findings predict a therapeutic potential of piperine against cognitive deficits in sAD mouse. This effect might be due to its abilities to ameliorate oxidative-nitrosative stress, restore neurotransmission and reduce neuroinflammation.

Topics: Alkaloids; Alzheimer Disease; Animals; Benzodioxoles; Cognition Disorders; Disease Models, Animal; Hippocampus; Inflammation; Infusions, Intraventricular; Male; Maze Learning; Memory Disorders; Mice; Neuroprotective Agents; Nitrogen; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Streptozocin