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March 21, 2026Molecular Neurobiology0 citationsOpen Access

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

EDElif Azize Özşahin Delibaş ZAZeynep Kasap Acungil EKEsra KoçTokat Gaziosmanpaşa Üniversitesi

Key Points

This research aims to evaluate the neuroprotective effects of chalcone-based pyrazoline derivatives on neuroinflammation and oxidative stress in epilepsy.
Utilized a penicillin-induced epilepsy model in rats.
Administered chalcone-based pyrazoline derivatives (CCA-326, CCA-334, CCD-326, CCD-334).
Measured brain and plasma levels of COX-2, 5-LOX, NF-κB, KEAP1, and NRF2 using the ELISE method.
Determined total antioxidant status (TAS) and total oxidant status (TOS) through colorimetric methods.
CCA-326 and CCA-334 significantly reduced levels of NF-κB, COX-2, and 5-LOX.
Increased NRF2 expression and TAS levels were observed.
Notable decrease in KEAP1 levels indicated enhanced activation of the antioxidant system.
CCA-334 emerged as a promising compound for targeting oxidative stress and inflammation in 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.

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