Chalcone-based Pyrazoline Derivatives as Modulators of Neuroinflammatory and Redox Pathways in Experimental Epilepsy

Abstract

Epilepsy is a chronic neurological condition characterized by complex pathophysiological interactions involving oxidative stress (OS) and neuroinflammation. In this study, the neuroprotective effects of chalcone-based pyrazoline derivatives (CCA-326, CCA-334, CCD-326, and CCD-334) are investigated in a penicillin-induced epilepsy model in rats. The ELISE method is used to measure the effects of these compounds on the plasma and brain levels of cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), nuclear factor-kappa B (NF-κB), Kelch-like ECH-associated protein 1 (KEAP1), and nuclear factor erythroid 2-related factor 2 (NRF2). Total antioxidant status (TAS) and total oxidant status (TOS) were determined using colorimetric methods. CCA-326 and CCA-334 significantly reduces NF-κB, COX-2, and 5-LOX levels, increases NRF2 expression and TAS levels, and supports the activation of the endogenous antioxidant system by inducing a noticeable decrease in KEAP1 levels. These results suggest that CCA-334 stands out as a promising compound for further investigation targeting oxidative stress and inflammation in epilepsy, and that chalcone-based pyrazoline derivatives may modulate key inflammatory and redox pathways involved in epileptogenesis.