Antiepileptic effect of curcumin by activating the Nrf2/HO-1 pathway in the brains of epileptic mice using an α-ketoester-based H2O2-activatable fluorescent probe

Epilepsy is a chronic brain disease with various causes, among which oxidative stress-induced neuronal damage is a significant pathological factor and has been widely studied as one of the key pathogenic mechanisms. Hydrogen peroxide (H₂O₂), a representative reactive oxygen species (ROS), plays an important role in epilepsy. However, real-time imaging capable of revealing the distribution of H₂O₂ in the living brain remains limited. To address this, we developed a feasible fluorescent probe library based on the unique reaction between the α-ketoester moiety and H₂O₂, combined with dicyanoisophorone derivatives possessing excellent optical performance. In consequence, DCI-BT-PY was optimized as a novel fluorescent probe for H₂O₂ through parallel testing of its physicochemical and optical properties. Notably, due to its good blood-brain barrier (BBB) penetration, DCI-BT-PY was used to monitor H₂O₂ upregulation in the brains of epileptic mice, revealing a close relationship between H₂O₂ and epilepsy. Furthermore, using the Sombati epilepsy model of hippocampal neuronal cells and the mouse model of epilepsy, the neuroprotective effect of curcumin on oxidative stress injury of nerve cells was explored, showing that it may alleviate epilepsy by activation of the Nrf2/HO-1 signaling pathway for suppressing the neurotoxic damage. This finding offers new insights into the pathogenesis and treatment of epilepsy. Additionally, this work provides a reliable tool for evaluating H 2 O 2 fluctuations in the brains of epilepsy-induced mice, thereby establishing a solid foundation for antioxidant therapies targeting epilepsy.