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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-\u03baB), 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-\u03baB, 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.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s12035-026-05795-y","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:22:31Z","timestamp":1773854551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chalcone-based Pyrazoline Derivatives as Modulators of Neuroinflammatory and Redox Pathways in Experimental Epilepsy"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-0884","authenticated-orcid":false,"given":"Elif Azize \u00d6z\u015fahin","family":"Deliba\u015f","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-7628","authenticated-orcid":false,"given":"Zeynep Kasap","family":"Acungil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-608X","authenticated-orcid":false,"given":"Esra","family":"Ko\u00e7","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1783-3618","authenticated-orcid":false,"given":"\u015eeyma","family":"\u00d6zsoy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"issue":"10","key":"5795_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11102825","volume":"11","author":"L Palumbo","year":"2023","unstructured":"Palumbo L, Carinci M, Guarino A, Asth L, Zucchini S, Missiroli S, Rimessi A, Pinton P, et al. 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