{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:35:49Z","timestamp":1791513349130,"version":"4.3.4"},"reference-count":70,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oregon Partnership for Alzheimer\u2019s Research","award":["U19AT010829"],"award-info":[{"award-number":["U19AT010829"]}]},{"name":"Oregon Partnership for Alzheimer\u2019s Research","award":["S10RR027878"],"award-info":[{"award-number":["S10RR027878"]}]},{"name":"Oregon Partnership for Alzheimer\u2019s Research","award":["S10OD026922"],"award-info":[{"award-number":["S10OD026922"]}]},{"DOI":"10.13039\/100008460","name":"NIH","doi-asserted-by":"publisher","award":["U19AT010829"],"award-info":[{"award-number":["U19AT010829"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"NIH","doi-asserted-by":"publisher","award":["S10RR027878"],"award-info":[{"award-number":["S10RR027878"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"NIH","doi-asserted-by":"publisher","award":["S10OD026922"],"award-info":[{"award-number":["S10OD026922"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["U19AT010829"],"award-info":[{"award-number":["U19AT010829"]}]},{"name":"NIH","award":["S10RR027878"],"award-info":[{"award-number":["S10RR027878"]}]},{"name":"NIH","award":["S10OD026922"],"award-info":[{"award-number":["S10OD026922"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Withania somnifera (WS), also known as ashwagandha, is a popular botanical supplement used to treat various conditions including memory loss, anxiety and depression. Previous studies from our group showed an aqueous extract of WS root (WSAq) enhances cognition and alleviates markers for depression in Drosophila. Here, we sought to confirm these effects in the 5xFAD mouse model of \u03b2-amyloid (A\u03b2) accumulation. Six- to seven-month-old male and female 5xFAD mice were treated with WSAq in their drinking water at 0 mg\/mL, 0.5 mg\/mL or 2.5 mg\/mL for four weeks. In the fourth week of treatment, spatial memory, anxiety and depressive-like symptoms were evaluated. At the conclusion of behavioral testing, brain tissue was harvested, immunohistochemistry was performed, and the cortical expression of antioxidant response genes was evaluated. Both concentrations of WSAq improved spatial memory and reduced depressive and anxiety-related behavior. These improvements were accompanied by a reduction in A\u03b2 plaque burden in the hippocampus and cortex and an attenuation of activation of microglia and astrocytes. Antioxidant response genes were upregulated in the cortex of WSAq-treated mice. Oral WSAq treatment could be beneficial as a therapeutic option in AD for improving disease pathology and behavioral symptoms. Future studies focused on dose optimization of WSAq administration and further assessment of the mechanisms by which WSAq elicits its beneficial effects will help inform the clinical potential of this promising botanical therapy.<\/jats:p>","DOI":"10.3390\/antiox13101164","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T04:05:46Z","timestamp":1727323546000},"page":"1164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Withania somnifera (Ashwagandha) Improves Spatial Memory, Anxiety and Depressive-like Behavior in the 5xFAD Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Noah","family":"Gladen-Kolarsky","sequence":"first","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-0423","authenticated-orcid":false,"given":"Olivia","family":"Monestime","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Bollen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"},{"name":"BENFRA Botanical Dietary Supplements Research Center, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaewoo","family":"Choi","sequence":"additional","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Portland, OR 97239, USA"},{"name":"Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Yang","sequence":"additional","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Portland, OR 97239, USA"},{"name":"Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4731-0247","authenticated-orcid":false,"given":"Armando Alcazar","family":"Maga\u00f1a","sequence":"additional","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Portland, OR 97239, USA"},{"name":"Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA"},{"name":"Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia S.","family":"Maier","sequence":"additional","affiliation":[{"name":"BENFRA Botanical Dietary Supplements Research Center, Portland, OR 97239, USA"},{"name":"Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA"},{"name":"Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-6453","authenticated-orcid":false,"given":"Amala","family":"Soumyanath","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"},{"name":"BENFRA Botanical Dietary Supplements Research Center, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora E.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA"},{"name":"BENFRA Botanical Dietary Supplements Research Center, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). 2023 Alzheimer\u2019s disease facts and figures. 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