Hypericum perforatum L. (genus Hypericum, family Hypericaceae), a plant commonly used in traditional Chinese medicine, is believed to confer a wide range of benefits, including fever reduction, detoxification, calming, and pain relief via decoctions of its stems and leaves. Hyperoside (HYP), a natural compound extracted from Hypericum perforatum L., has been shown to demonstrate a wide array of bioactivities including antioxidative, anti-inflammatory, and anti-apoptotic effects. In this study, we investigated the effects of HYP on epilepsy-induced neuronal damage in mice and the associated regulatory factors.This study examined the potential therapeutic use of HYP for the treatment of neuronal damage in a mouse model of epilepsy and explored the relationships of the potential neuroprotective effects of HYP pretreatment with antioxidant levels and autophagy.ICR mice were randomly divided into six groups: sham group, sham-HYP group, KA group, KA-HYP group, KA-HYP-DDC group and KA-CQ group. Immunohistochemical staining was used to assess changes in NeuN, IBA-1, and GFAP expression in the CA3 region of the hippocampus. Immunofluorescence staining was used to assess the effects of HYP on the number of autophagosomes that accumulated in neurons in the hippocampal CA3 region. The levels of SOD1, SOD2, LC3I/II, Beclin1, and PI3K/AKT and MAPK signaling-related proteins were detected by Western blot.Pretreatment with 50 mg/kg HYP protected against epilepsy-induced neuronal damage in the hippocampal CA3 region. Additionally, HYP enhanced antioxidant levels and reduced the levels of autophagy-related proteins via the PI3K/AKT and MAPK pathways.HYP protected the hippocampal CA3 region against epilepsy-induced neuronal damage via enhancing antioxidant levels and reducing autophagy. The mechanism of action may be related to the maintenance of antioxidant levels and the suppression of autophagy via the PI3K/Akt and MAPK pathways.
