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The causes are yet unknown, except from advanced age and genetic predisposition. Natural products provided advantageous advantages for managing AD due to their efficacy, safety, and accessibility. The memory boosting effects of chemically characterized <jats:italic>Ipomoea carnea<\/jats:italic> ethanol extract (IPC-EtOH) on behavioral, biochemical, histological, and molecular levels against cognitive impairment induced by AlCl<jats:sub>3<\/jats:sub> exposure in rats were assessed using donepezil as a reference drug. Behavioral tests (spontaneous alternation T-maze and open field test) and assays for GSK3\u03b2, CREB, FOXO1a, \u03b2-secretase, tau, oxidative stress biomarkers, histopathology, and immunohistochemistry for cyclooxygenase 2 (COX-2) were conducted. The chemical profiling of IPC-EtOH using UPLC-ESI\u2013qTOF-MS coupled with molecular networking revealed the identification of 83 bioactive metabolites, including pyrrolizidine alkaloids and cinnamic acid derivatives which previously undescribed from this species. AlCl<jats:sub>3<\/jats:sub> injection significantly elevated tau, <jats:italic>\u03b2<\/jats:italic>-secretase, GSSG, GSK-3<jats:italic>\u03b2<\/jats:italic>, and FOXO3a levels and down regulated CAT, SOD, and CREB, with strong COX-2 immunoexpression in the cortex and hippocampus compared to controls. Oral co-administration of donepezil or IPC-EtOH to AlCl<jats:sub>3<\/jats:sub>-treated rats restored near-normal function in these brain regions, significantly attenuating spatial learning, memory, and locomotor impairments. These results suggest that IPC-EtOH could be a promising therapy for mitigating aluminum-induced neurotoxicity, though further studies are needed to elucidate its precise mechanisms of action. These outcomes emphasize <jats:italic>I. carnea<\/jats:italic> ethanol extract\u2019s potential as an appealing therapy for AD by demonstrating its neuroprotective and memory-enhancing properties in rats having AlCl<jats:sub>3<\/jats:sub>-induced memory impairment.<\/jats:p>","DOI":"10.1007\/s10787-025-01687-0","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T11:38:58Z","timestamp":1741779538000},"page":"2043-2068","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Unveiling the neuroprotective potential of Ipomoea carnea ethanol extract via the modulation of tau and \u03b2-secretase pathways in AlCl3-induced memory impairment in rats in relation to its phytochemical profiling"],"prefix":"10.1007","volume":"33","author":[{"given":"Walaa A.","family":"El-Kashak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed F.","family":"Essa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed F.","family":"Abdelhameed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine H.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa S.","family":"Abd Elkarim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai M.","family":"Elghonemy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassant M. 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