Piperine Improves Learning Deficit Through Modulation of Wnt/Β-Catenin Signaling Pathway: Involvement of the Dorsal Hippocampus Serotonin-1A Receptors Publisher Pubmed



A Ghasemi ALI ; A Saadinezhad AMIRHOSSEIN ; S Halallkhor SOHHRAB ; F Sadeghi F ; Sm Hosseini Seyed MOHAMMAD ; M Karami MAHMOUD ; S Hosseinzadeh SOHEILA
Source: European Journal of Pharmacology Published:2025

Abstract

Background: In the hippocampal region, piperine raised serotonin levels. Nevertheless, little is currently understood about how piperine acts through the Wnt/β-catenin pathway and regulates neurogenesis. Methods: Electroencephalogram electrodes were implanted in the frontoparietal and hippocampal regions of a streptozotocin (STZ)-induced rat model of Alzheimer's disease (AD). The involvement of serotonin-1A receptors in hippocampus was evaluated by microinjection of 1 μL of [8-hydroxy-2-(di-n-propylamino) tetralin (8OH-DPAT)/N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane-carboxamide (WAY-100635), in the mediation of the behavioral effects of piperine at 1, 10, and 50 μg/ml, 30 min before the probe trial and before recording. The left hemisphere was placed in 10 % formalin to make a tissue incision. To identify potential genes regulated by the Wnt/β-catenin pathway, the right hippocampal tissue was dissected on a cold phosphate-buffered saline plate and stored in the freezer. Results: Memory-enhancing effect of piperine at 50 μg/ml, was efficiently prevented by the 8OH-DPAT. Moreover, the animals in the Saline/8OH, AD/Pip50, and AD/WAY/Pip50 groups demonstrated notably higher mean absolute power in theta, beta, and gamma frequencies than the AD/Tween, AD/8OH, and AD/8OH/Pip50. Neuroprotection was induced morphologically in the dentate gyrus following co-administration of WAY-100635 and 50 μg/ml of piperine. The expression of serum- and glucocorticoid-inducible kinase 1 was significantly higher in the AD/Tween and AD/8OH groups than the Saline/8OH groups. The administration of WAY-100635 and piperine 50, markedly increased the expression of the c-myc gene. Conclusions: Understanding more about the signal transduction pathways associated with piperine may develop a strategy for treating symptoms and pathological conditions related to AD. © 2025 Elsevier B.V., All rights reserved.