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(Lamiaceae) is a shrub traditionally used as a medicinal plant to treat inflammation, skin diseases, and bronchitis. This study aims to identify the main bioactive metabolites in <jats:italic>C. infortunatum<\/jats:italic> using LC-QTOF-MS\/MS and investigate its potential in protecting against cognitive decline in rats with scopolamine-induced AD disease. Metabolite profiling was performed on the methanol extract of the plant\u2019s aerial parts using LC-QTOF-MS\/MS. The inhibitory activity of the acetylcholinesterase enzyme was measured <jats:italic>in vitro.<\/jats:italic> To evaluate the cognitive effects, the methanol extract was orally administered at three doses (100, 200, and 400\u00a0mg\/kg) to scopolamine-induced AD rats, and their cognitive functions were assessed using the novel object recognition test. Additionally, acetylcholinesterase enzyme activity, as well as the levels of acetylcholine, dopamine, noradrenaline, glutathione, malondialdehyde, tumor necrosis factor-\u03b1, interleukin-1\u03b2, and amyloid-\u03b2 in the rat hippocampus, were measured using ELISA, followed by histopathological evaluation. A total of 79 metabolites, spanning various chemical classes, such as organic acids, phenolic acids, phenylpropanoids and phenylethanoids, flavonoids, coumarins, other phenolics, and fatty acids and their derivatives, were identified. The results showed that the extract promoted enhanced cognitive functions in the novel object recognition test. Scopolamine administration significantly altered the acetylcholinesterase enzyme activity and biomarker levels in the rat\u2019s hippocampus. However, treatment with <jats:italic>C. infortunatum<\/jats:italic> at 200 and 400\u00a0mg\/kg almost restored these neurotransmitter levels to normal, which was further confirmed by histopathological analysis. This study demonstrates the therapeutic potential of <jats:italic>C. infortunatum<\/jats:italic> in mitigating cognitive decline in AD, with its first metabolite profiling revealing a range of bioactive compounds. The extract improved cognitive function in scopolamine-induced AD rats, restored acetylcholinesterase activity, normalized neurotransmitter levels, and reduced oxidative stress and inflammation. These findings suggest that <jats:italic>C. infortunatum<\/jats:italic> is a promising candidate for the development of natural therapies targeting AD.<\/jats:p>","DOI":"10.1038\/s41598-024-82265-2","type":"journal-article","created":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T11:43:01Z","timestamp":1736077381000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A comprehensive investigation of Clerodendrum Infortunatum Linn. using LC-QTOF-MS\/MS metabolomics as a promising anti-alzheimer candidate"],"prefix":"10.1038","volume":"15","author":[{"given":"Fatma","family":"Atef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa A.","family":"Abdelkawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma M.","family":"Eltanany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Fayez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed F.","family":"Abdelhameed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Benavente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inas Y.","family":"Younis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa M.","family":"Otify","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,5]]},"reference":[{"key":"82265_CR1","doi-asserted-by":"crossref","unstructured":"Nichols, E. et al. 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