Abstract
Treatment with valproic acid (VPA) can induce oxidative stress, leading to neuronal degeneration. Hesperidin (HSD) has an antioxidant function that can mitigate oxidative stress, thereby promoting hippocampal neurogenesis. Because brain function and memory are reliant on hippocampal neurogenesis, this work is planned to elucidate the effects of HSD on the VPA-induced alterations in hippocampal neurogenesis and apoptosis via oxidative damage. Twenty-four male Sprague-Dawley rats were grouped into the vehicle, VPA, HSD, and VPA + HSD groups. After administration, the hippocampi and prefrontal cortex were harvested for p21 staining, assessment of MDA, CAT, SOD, and GPx, and Western blotting analysis of Nrf2, Bax, caspase3, and Bcl-2 proteins. The results exhibited a significantly elevated level of p21-positive cells in VPA-treated rats, indicating cell cycle arrest in hippocampal neurogenesis. Additionally, our findings demonstrated a notable rise in oxidative stress, a decrease in antioxidant enzyme activity and the transcription factor Nrf2 in VPA-treated rats. Furthermore, VPA induced apoptotic activities, as substantiated by the upregulation of Bax and caspase3, and the downregulation of Bcl-2. These findings demonstrate that HSD can reduce oxidative stress levels, thereby mitigating the arrest of the cell cycle and apoptotic activity induced by VPA treatment in both the hippocampus and prefrontal cortex.