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We conducted chromatographic and bioassay-guided fractionation of <jats:italic>D. viscosa<\/jats:italic> root extract to isolate a specific fraction (fraction \u201cK\u201d) with antidepressant-like characteristics in vivo and strong antioxidant properties in vitro. A single dose of \u201cK\u201d reduced immobility time in the forced swim test with a mouse model possessing a depressive-like phenotype. Neurochemical profiling for 5-hydroxytryptamine (5-HT) and its primary metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in prefrontal cortex and hippocampus of \u201cK\u201d-treated mice showed reduction in 5-HIAA, indicative of either serotonin uptake transporter or monoamine oxidase-A inhibition, as well as slight increases in 5-HT content. These neurochemical alterations, as well as the behavioral changes observed, were comparable to the effects of paroxetine. \u201cK\u201d also protected PC12 cells in a H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> cytotoxicity assay, thus demonstrating antioxidant properties, yet paroxetine augmented oxidative damage and cell death. Identification of the main compounds in \u201cK\u201d by high-performance liquid chromatography-tandem mass spectrometry (HPLC\u2013MS\/MS) indicated that chlorogenic acid and cynarine comprised 87% of the total components. <jats:italic>D. viscosa<\/jats:italic> root extract appears to produce antidepressant and cytoprotective effects and may serve as an attractive alternative to standard therapies for depression.<\/jats:p>","DOI":"10.1038\/s41598-022-04840-9","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T11:06:11Z","timestamp":1646651171000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Antidepressant-like effects of a chlorogenic acid- and cynarine-enriched fraction from Dittrichia viscosa root extract"],"prefix":"10.1038","volume":"12","author":[{"given":"Kateryna","family":"Murlanova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Netanela","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pinkus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudmila","family":"Vinnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Pletnikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kirby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Gorelick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyashiv","family":"Drori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Pinhasov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"4840_CR1","unstructured":"World Health Organization, Depression and Other Common Mental Disorders: Global Health Estimates. 2017, World Health Organization; Licence: CC BY-NC-SA 3.0 IGO."},{"issue":"15","key":"4840_CR2","first-page":"1517","volume":"317","author":"MJ Friedrich","year":"2017","unstructured":"Friedrich, M. 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