Pre- and post-treatment with apigenin attenuates status epilepticus-induced neuronal death by reducing oxidative stress and inflammation in the mouse brain

Status epilepticus (SE) is a prolonged, recurrent seizure leading to neuronal damage. Given the limitations of existing treatment modalities, exploring new alternatives is imperative. Emerging research suggests that inflammatory processes are implicated in epileptogenesis. Apigenin (AP), an antioxidant and anti-inflammatory flavonoid, demonstrates neuroprotective effects in brain disorders. Nevertheless, its significance in status epilepticus remains unstudied. Therefore, we investigated whether AP alleviates pilocarpine (PLO)-induced SE neuropathology. We propose that AP may reduce SE by attenuating oxidative stress, inflammation, blood-brain barrier (BBB) disruption, and neurodegeneration. Adult Swiss albino mice were administered AP (75 mg/kg, orally) either for eight days preceding SE or for an additional three days after SE induction by PLO injection (320 mg/kg, i.p.). Following PLO administration in AP, diazepam (standard), or saline-treated (control) mice, the onset and duration of convulsion were recorded for two hours. Mice were euthanized three days post-SE induction, and brains were collected for analysis, including oxidative stress markers, cytokines assays, BBB permeability using Evans blue, and Fluorjade C staining. Behavioral studies demonstrated that pre- and post-AP treatment reduced seizure severity in mice compared to controls. AP attenuated SE-induced BBB permeability, oxidative stress (SOD, CAT, GSH, and MDA levels), and neuronal cell death. Furthermore, we observed a suppression of TNF-α and IL-6 cytokines levels in AP-treated mice brains. Although pre-treatment with AP reduced seizure susceptibility, post-treatment ameliorated this condition with neuroprotection. Our findings highlight the multifaceted neuroprotective effects of AP in mitigating SE, suggesting it is a potential therapeutic agent for SE and associated neurological disorders.