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We investigated the potential of Heracleum moellendorffii Hance root extract (HME) for treating alcohol-related cognitive impairment. Behavioral tests evaluated the effects of HME on cognitive function and depression. Changes in hippocampus and liver tissues were evaluated by Western blotting and H&amp;E staining. The group treated with HME 200 mg\/kg showed a significant increase in spontaneous alternation in Y-maze and a decrease in immobility in a forced swimming test (FST) compared to the vehicle-treated group. These results suggest that HME can restore memory deficits and reverse depressive symptoms caused by chronic alcohol consumption. The HME-treated group also upregulated brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1\/2 (ERK1\/2), and phosphorylated cAMP response element-binding protein (CREB) in the hippocampus. Additionally, it reduced lipid vacuolation in the liver and increased the expression of aldehyde dehydrogenase 1 (ADH1). The administration of HME improves cognitive impairment and reverses depressive symptoms due to alcohol consumption, restoring neural plasticity in the hippocampus and alcohol metabolism in the liver. These findings suggest that HME is a promising treatment for alcohol-related brain disorders. Molecular mechanisms underlying the therapeutic effects of HME and its active ingredients should be investigated further.<\/jats:p>","DOI":"10.3390\/ijms25158526","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T18:21:40Z","timestamp":1722882100000},"page":"8526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protective Effects and Mechanism of Heracleum moellendorffii Hance on Alcohol-Induced Cognitive Decline in Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Woohee","family":"Park","sequence":"first","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2286-1242","authenticated-orcid":false,"given":"Yunna","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, College 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":[{"role":"author","vocabulary":"crossref"}]},{"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":"Department of Neuropsychiatry, College 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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1016\/S0140-6736(17)31363-6","article-title":"Dementia Prevention, Intervention, and Care","volume":"390","author":"Livingston","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hermens, D.F., and Lagopoulos, J. 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