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Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Major depressive disorder (MDD) is a leading contributor to disability worldwide, yet current antidepressant treatments remain limited by incomplete remission, treatment resistance, and adverse effects. 20-glucoginsenoside Rf (20-gluco-Rf), a trace bioactive saponin derived from Panax ginseng, has not been sufficiently investigated in depression-related experimental models. In this study, we evaluated the antidepressant potential of 20-gluco-Rf in a mouse model established by prefrontal cortex (PFC) infusion of L-alpha-aminoadipic acid (L-AAA), an astrocyte-selective gliotoxin. Oral administration of 20-gluco-Rf, vehicle, or fluoxetine was initiated before L-AAA infusion into the PFC. 20-Gluco-Rf significantly reduced immobility time in the forced swim and tail suspension tests compared with vehicle treatment. Furthermore, 20-gluco-Rf improved performance in the novel object recognition test. These behavioral changes were accompanied by reduced mRNA expression of proinflammatory mediators, including IL-1\u03b2, IL-6, TNF-\u03b1, and lipocalin-2, as well as changes in GFAP and IBA-1 protein expression in the PFC. Collectively, these findings provide preliminary in vivo evidence that 20-gluco-Rf is associated with antidepressant-like and cognition-related behavioral effects in an L-AAA-induced mouse model, accompanied by changes in neuroinflammatory and glial-associated molecular markers.<\/jats:p>","DOI":"10.3390\/cimb48090920","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:24:02Z","timestamp":1788945842000},"page":"920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antidepressant Effects of 20-Glucoginsenoside Rf in an L-AAA-Induced Mouse Model with Glial-Associated Molecular Alterations"],"prefix":"10.3390","volume":"48","author":[{"given":"Sangbeom","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0627-768X","authenticated-orcid":false,"given":"Seung-Hun","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Neuropsychiatry of Korean Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Research Group of Neuroscience, East-West Medical Research Institute, WHO Collaborating Center, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1192\/bjp.2024.266","article-title":"Global, regional and national burden of depressive disorders and attributable risk factors, from 1990 to 2021: Results from the 2021 Global Burden of Disease study","volume":"227","author":"Rong","year":"2025","journal-title":"Br. 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