DOI: 10.3390/ijms27198579 ISSN: 1422-0067

Neuroprotective Effects of Pinostrobin in a Rat Model of Kainic Acid-Induced Epilepsy

Jinatta Jittiwat, Ratchaniporn Kongsui, Tichanon Promsrisuk, Napatr Sriraksa, Sitthisak Thongrong

Epilepsy is a serious neurological disorder characterized by recurrent seizures and neuronal loss. Prolonged seizure activity is associated with changes in apoptosis-related proteins, including Bcl-2-associated X protein (Bax) and caspase-3, as well as alterations in microglial and astroglial responses. This study investigated the neuroprotective effects of pinostrobin, a bioflavonoid, in a kainic acid (KA)-induced epilepsy model and examined its effects on apoptosis-related proteins. Pinostrobin (40 mg/kg) was administered orally once daily for 7 days before and 14 days after intracerebroventricular injection of KA. KA injection resulted in neuronal cell loss, increased number of ionized calcium-binding adapter molecule 1 (Iba1)-positive microglia, and reactive astrocytosis in the cornu ammonis 1 (CA1), cornu ammonis 3 (CA3), and hilar regions. These changes were accompanied by decreased levels of protein kinase B (Akt), phosphorylated-Akt (p-Akt), and the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), together with increased levels of Bax and caspase-3. Pinostrobin treatment significantly attenuated neuronal cell loss, reduced the number of Iba1-positive microglia, and increased glial fibrillary acidic protein (GFAP) immunoreactivity in the CA1, CA3, and hilar regions. Moreover, pinostrobin increased Akt, p-Akt, and Bcl-2 levels while decreasing Bax and caspase-3 levels. Collectively, these findings suggest that pinostrobin has potential neuroprotective effects in the KA-induced epilepsy model and is associated with changes in apoptosis-related proteins and glial responses.