Document Type : Original Article

Authors

• Seyedeh Ommolbanin ا Ghasemian ¹
• Yasin Deravipoor ²
• Asiye ا Seyyed ³

¹ 2.*Department of Veterinary, Be.C., Islamic Azad University, Behbahan, Iran. ORCID: orcid.org/0000-0002-4805-3553 Department of Veterinary, Be.C., Islamic Azad University, Behbahan, Iran

² Department of Veterinary, Be.C., Islamic Azad University, Behbahan, Iran. University, Behbahan, Iran

³ 3- Department of Sport Physiology, Be.C., Islamic Azad University, Behbahan, Iran.

Abstract

Alzheimer’s disease (AD) is associated with β-amyloid (Aβ) accumulation, synaptic dysfunction, and progressive neuronal degeneration. The PI3K/AKT/FOXO3 signaling axis plays a key role in 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 gene expression in an experimental Aβ-induced AD-like model.

Forty-eight male Wistar rats were randomly allocated into six groups, and an AD-like condition was induced by stereotaxic injection of Aβ1–42 into the CA1 region of the hippocampus. The endurance training intervention was performed for eight weeks, while black pepper extract was administered orally (187.5 mg/kg/day). Gene expression levels were quantified using quantitative real-time PCR (qRT-PCR), and data were analyzed using one-way ANOVA.

Aβ injection significantly downregulated PI3K and AKT1 and upregulated FOXO3 compared with the control group (P < 0.05). Although endurance training or black pepper extract alone partially attenuated these alterations, the combined intervention produced a stronger modulatory effect by significantly increasing PI3K and AKT1 expression and reducing FOXO3 expression toward control levels.

Overall, these findings suggest that combining high-intensity endurance training with black pepper extract modulates hippocampal PI3K/AKT/FOXO3 pathway-related gene expression in an Aβ-induced AD-like condition, indicating a potential neuroprotective molecular mechanism that warrants further confirmation using protein-level, histological, and behavioral outcomes.

Keywords

• Alzheimer’s disease
• High intensity endurance training
• Black pepper extract
• Piperine
• PI3K/AKT/FOXO3
• Gene expression

Main Subjects

• Cell and Molecular Biology