Xanthohumol Alleviates Epileptic Seizures in Pentylenetetrazol-Induced Convulsions in Mice by Regulating Inflammation and Oxidative Stress

Abstract

Background: Epilepsy is a prevalent neurobehavioral disorder, which affects more the 50 million individuals worldwide. It is characterized by neuron hyperexcitability mediated by repetitive convulsions. The current investigation was planned to study the therapeutic properties of the xanthohumol against pentylenetetrazol (PTZ)-induced convulsions in mice by regulating inflammation and oxidative stress. Methods: The 70 mg/kg of PTZ was administered (i.p.) to the mice for stimulating the epileptic seizures and 20 mg/kg of xanthohumol was pre-treated by oral route before the 30 min of PTZ administration. The mice were observed closely for 30 min after the PTZ treatment to detect the onset and duration of clonic/tonic convulsions and mortality. The status of glutamate, GABA, dopamine, Na+K+ATPase, and Ca+ATPase were quantified using respective kits. The level of MDA, NO, GSH, and SOD were detected using standard methods. The levels of inflammatory biomarkers such as COX-2, TNF-α, NF-κB, TLR-4, and IL-1β in the brain tissues were inspected using kits. The histopathological analysis was done on the brain tissues. Results: The xanthohumol significantly (p < 0.05) reduced the onset and duration of convulsions, mortality, and behavioral changes in the epileptic mice. The levels of COX-2, TNF-α, NF-κB, TLR-4, and IL-1β were significantly (p < 0.05) decreased in the epileptic mice by 20 mg/kg xanthohumol treatment. The levels of MDA and NO was reduced and GSH and SOD were increased by the 20 mg/kg xanthohumol treatment. The 20 mg/kg xanthohumol significantly (p < 0.05) decreased the glutamate and improved the dopamine, GABA, Na+K+ATPase, and Ca+ATPase in the epileptic mice. The findings of histopathological studies revealed that 20 mg/kg xanthohumol decreased the inflammatory signs and pyknosis in the brain tissues. Conclusion: Pre-treatment with the 20 mg/kg xanthohumol ameliorates the PTZ-triggered seizures in a mice model through its antioxidant and anti-inflammatory potentials. Hence, xanthohumol can be a promising antiepileptic candidate in the future to treat epilepsy.