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Based on the described antioxidant activity of naturally occurring flavonoids, this study evaluated the antioxidant mechanisms of the flavonoid naringenin and the senecioic acid ester derivatives in cortical astrocytes. Naringenin and (S)-naringenin were purified from Citrus paradisi, and from them 7,4-O-disenecioic ester naringenin, (S)-7,4-O-disenecioic ester naringenin, and 7-O-senecioic ester naringenin were synthesized and tested for antioxidant activity by the free-radical scavenging reaction with DPPH. The flavonoids\u2019 toxicity and glutathione (GS) depletion were determined in rat astrocyte cultures; the effects on the astrocytes\u2019 reactivity was determined by the expression of the glial fibrillary acidic protein (GFAP) and by measuring nitric oxide (NO) production in astrocytes treated with lipopolysaccharide (LPS, 1 \u00b5g\/mL\/24 h). The compounds (1\u201310 \u03bcM) presented antioxidant effects, and the (S)-7,4\u2032-O-disenecioic ester naringenin was the most effective. The compounds (1\u2013100 \u03bcM) were not toxic to the astrocytes, also promoting an antioxidant effect by increasing GSH. Moreover, naringenin, (S)-7,4\u2032-O-disenecioic ester naringenin, and 7-O-senecioc ester naringenin mitigated the astrocyte reactivity induced by LPS, reducing GFAP expression and NO production. These findings indicate that naringenin and senecioic acid ester derivatives present a pharmacological potential as antioxidant and anti-inflammatory compounds for brain diseases via the modulation of astrocyte response.<\/jats:p>","DOI":"10.3390\/ijms26052215","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T04:10:42Z","timestamp":1740975042000},"page":"2215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis of Naringenin and Senecioic Acid Ester Derivatives and Biological Evaluation of the Astrocyte Antioxidant Mechanism and Reactivity After Inflammatory Stimulus"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9851-1615","authenticated-orcid":false,"given":"Jana\u00edna Ribeiro Pereira","family":"Soares","sequence":"first","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleonice Creusa","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-5566","authenticated-orcid":false,"given":"Lucas Matheus Gon\u00e7alves","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Her\u00e1clito","family":"Rocha Neto","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1236-1973","authenticated-orcid":false,"given":"Maur\u00edcio Moraes","family":"Victor","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador 40170-115, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elivana Lima","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Federal Institute of Bahia, Campus Vit\u00f3ria da Conquista, Vit\u00f3ria da Conquista 45078-300, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-2893","authenticated-orcid":false,"given":"Maria de F\u00e1tima Dias","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, Brazil"},{"name":"National Institute of Translational Neuroscience (INNT), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8975-3871","authenticated-orcid":false,"given":"Silvia Lima","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S\/N, Salvador 40231-300, Brazil"},{"name":"National Institute of Translational Neuroscience (INNT), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5642-9170","authenticated-orcid":false,"given":"Juciele Valeria Ribeiro","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Av. 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