Introduction: Alzheimer’s disease (AD) is associated with β-amyloid (Aβ) accumulation, synaptic dysfunction, and progressive neuronal degeneration. The PI3K/AKT/FOXO3 signaling axis contributes to neuronal survival, oxidative stress regulation, and apoptosis, and its dysregulation has been implicated in AD-related neurodegeneration. This study investigated the effects of high-intensity endurance training and black pepper extract on hippocampal PI3K, AKT1, and FOXO3 mRNA expression in an experimental Aβ-induced AD-like model.
Methods: Forty-eight male Wistar rats were randomly assigned to six groups. An AD-like condition was induced by stereotaxic injection of Aβ1–42 into the CA1 region of the hippocampus. Endurance training was conducted for eight weeks, and black pepper extract was administered orally at 187.5 mg/kg/day. Hippocampal PI3K, AKT1, and FOXO3 mRNA expression levels were quantified using quantitative real-time PCR (qRT-PCR). Data were analyzed using one-way analysis of variance (ANOVA).
Results: Aβ injection significantly decreased PI3K and AKT1 mRNA expression and increased FOXO3 mRNA expression compared with the control group (P<0.05). Endurance training or black pepper extract administered individually partially attenuated these Aβ-associated changes. The combined intervention produced a greater alteration in gene expression, characterized by increased PI3K and AKT1 mRNA expression and decreased FOXO3 mRNA expression toward control levels.
Conclusion: The combination of high-intensity endurance training and black pepper extract was associated with changes in hippocampal PI3K, AKT1, and FOXO3 mRNA expression in the Aβ-induced AD-like model, suggesting a potential neuroprotective molecular response. However, these findings do not establish a causal effect on PI3K/AKT/FOXO3 signaling activity. Further studies incorporating functional assessments, including kinase activity, protein phosphorylation, apoptosis-related assays, and behavioral outcomes, are required to validate these molecular findings.