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Hence, this research aimed to investigate the potential neuroprotective impacts of the ethanolic extracts of\n                    <jats:italic>Citrus aurantium<\/jats:italic>\n                    unripe fruits and leaves (CAF and CAL, respectively) at doses 100 and 200\u00a0mg\/kg against cadmium chloride-provoked brain dysfunction in rats for 30 consecutive days. HPLC for natural pigment content revealed that CAF implied higher contents of Chlorophyll B, while the CAL has a high yield of chlorophyll A and total carotenoid. Fifty-seven chromatographic peaks were identified by UPLC\/MS\n                    <jats:bold>\/<\/jats:bold>\n                    MS; 49 and 29 were recognized from CAF or CAL, respectively. Four compounds were isolated from CAF: 3\u2019,4\u2019,7 \u2013trihydroxyflavone, isorhainetin, vitexin, and apigenin.\n                    <jats:italic>In vitro<\/jats:italic>\n                    studies outlined the antioxidant capacity of studied extracts where CAF showed better scavenging radical DPPH activity. Results clarified that both extracts with a superior function of CAF at the high adopted dose significantly ameliorated CdCl\n                    <jats:sub>2<\/jats:sub>\n                    -induced neuro-oxidative stress and neuro-inflammatory response via restoring antioxidant status and hindering nuclear factor kappa B (NF-\u03baB) stimulation. Moreover, it up-regulated the levels of phospho-protein kinase B (p-Akt), phospho- cAMP-response element binding protein (p-CREB), and brain-derived neurotropic factor (BDNF) levels, and elicited a marked decrease in the content of glycogen synthase kinase 3 beta (GSK3\u03b2), besides amending Caspase-3 and hyperphosphorylation of tau protein in brain tissues. Moreover, a significant improvement in the rats\u2019 behavioral tasks of the CAL and CAF-treated groups has been recorded, as indicated by marked preservation in locomotion, exploratory, and memory functions of the experimental rats. In conclusion, the reported neuroprotective impacts of\n                    <jats:italic>C. aurantium<\/jats:italic>\n                    extracts may be through modulating p-AKT\/p-CREB\/BDNF and \/ or p-Akt\/ GSK3\u03b2\/NF-\u03baB signaling pathways.\n                  <\/jats:p>","DOI":"10.1007\/s11011-024-01513-6","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T06:54:00Z","timestamp":1736146440000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Metabolomics analyses and comparative insight to neuroprotective potential of unripe fruits and leaves of Citrus aurantium ethanolic extracts against cadmium-induced rat brain dysfunction: involvement of oxidative stress and akt-mediated CREB\/BDNF and GSK3\u03b2\/NF-\u03baB signaling pathways"],"prefix":"10.1007","volume":"40","author":[{"given":"Doaa A. 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