{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:37:58Z","timestamp":1781303878691,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Stress is a major factor that threatens the body\u2019s homeostasis or well-being. Excessive stress causes psychological anxiety and tension, which disrupts the balance of the autonomic nervous system that maintains the body\u2019s balance, resulting in hormonal imbalance and brain changes. In this study, we investigated the effects of Withania somnifera (Ashwagandha) extract on depression, neurobehavior, and hippocampal changes in model mice exposed to stress. Using an excessive restraint stress-induced depression model, we measured the behavioral changes and the levels of brain-derived neurotrophic factor (BDNF) and antioxidant genes in five groups: control, stress, low-dose W. somniferous extract (20 mg\/kg\/day), high-dose W. somniferous extract (40 mg\/kg\/day), and L-theanine (50 mg\/kg\/day, positive control). Stressed mice showed poorer performance in the open field and elevated plus maze tests compared with the control group. The impaired performance was restored following W. somniferous extract administration. In addition, W. somniferous extract restored the decreased expression of BDNF in the hippocampus caused by restraint stress, improved the balance of stress hormones (i.e., cortisol, dopamine, and norepinephrine), and also regulated BDNF, inflammatory genes, and antioxidant genes in brain tissue. Therefore, W. somniferous extract can induce antidepressant and anti-stress effects by maintaining brain BDNF expression and preventing hippocampal tissue alterations caused by restraint stress.<\/jats:p>","DOI":"10.3390\/ijms26157317","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T10:25:34Z","timestamp":1753784734000},"page":"7317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Attenuation Effect of Withania somnifera Extract on Restraint Stress-Induced Anxiety-like Behavior and Hippocampal Alterations in Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-7373","authenticated-orcid":false,"given":"Kippuem","family":"Lee","sequence":"first","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22 Giheungdanji-ro, 24 Beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8258-119X","authenticated-orcid":false,"given":"Daehyeop","family":"Lee","sequence":"additional","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22 Giheungdanji-ro, 24 Beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-2871","authenticated-orcid":false,"given":"Joo Yun","family":"Kim","sequence":"additional","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22 Giheungdanji-ro, 24 Beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Jung","family":"Shim","sequence":"additional","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22 Giheungdanji-ro, 24 Beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Woo","family":"Bae","sequence":"additional","affiliation":[{"name":"3HLABS Co., Ltd., 240, Kintex-ro, Ilsanseo-gu, Goyang-si 10391, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"R&BD Center, hy Co., Ltd., 22 Giheungdanji-ro, 24 Beon-gil, Giheung-gu, Yongin-si 17086, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"FSO23","DOI":"10.4155\/fso.15.21","article-title":"The effects of chronic stress on health: New insights into the molecular mechanisms of brain\u2013body communication","volume":"1","author":"Mariotti","year":"2015","journal-title":"Futur. 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