CNS Neurol Disord Drug Targets. 2026 Jan 14. doi: 10.2174/0118715273423680251125073602. Online ahead of print.
ABSTRACT
INTRODUCTION: Sodium-glucose transport protein 2 (SGLT-2) inhibition regulates neuronal excitability by shifting glucose metabolism toward ketone utilization and by reducing oxidative stress and inflammation. Based on these mechanisms, this study investigated the anticonvulsant and anti-inflammatory effects of empagliflozin, a SGLT-2 inhibitor with neuroprotective properties, in a penicillin-induced epilepsy model.
METHODS: Thirty-five adult male Wistar rats were randomly divided into five groups (n = 7/group): sham, control (penicillin only), empagliflozin (10 mg/kg), diazepam (5 mg/kg), and empagliflozin + diazepam. Penicillin (500 IU) was administered intracortically to induce focal epileptiform activity. Electrocorticography (ECoG) recordings were obtained for 180 minutes to assess seizure latency, spike-wave frequency (SWF), and amplitude. Serum and cortical tissue levels of TNF-α, IL-6, and HMGB-1 were quantified using enzyme-linked immunosorbent assay (ELISA).
RESULTS: All treatment groups exhibited a statistically significant increase in latency to the first epileptiform activity compared to the control group. The empagliflozin group showed a marked reduction in SWF between 30 and 180 minutes, particularly during the 121-180-minute period. Tissue TNF-α levels were significantly lower in the empagliflozin + diazepam group compared to the control. Tissue IL-6 levels were lowest in the empagliflozin-only group, whereas serum IL-6 levels were significantly reduced in the combined treatment group. No significant differences in HMGB-1 levels were observed across groups.
DISCUSSION: Empagliflozin demonstrated anticonvulsant and anti-inflammatory effects by delaying seizure onset, reducing SWF, and modulating pro-inflammatory cytokine levels.
CONCLUSION: Empagliflozin demonstrated anticonvulsant and anti-inflammatory effects by delaying seizure onset, reducing SWF, and modulating pro-inflammatory cytokine levels. These findings suggest that empagliflozin may have therapeutic potential in epilepsy through SGLT-2 inhibition.
PMID:41574536 | DOI:10.2174/0118715273423680251125073602
