{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:55:32Z","timestamp":1773028532759,"version":"3.50.1"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011665","name":"Deanship of Scientific Research, King Saud University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>This study discovers the potential of hydroxychavicol\u2010enriched fraction of <jats:italic>Piper betle<\/jats:italic> L. leaf extract (HCRF) as an antidepressant alternative in chronic unpredictable mild stress (CUMS) rodent models with biochemical parameters. It also focused on possible mechanisms through molecular simulation via the anti\u2010inflammatory pathway and in silico pharmacokinetic study. HCRF is isolated from betel leaves, and Swiss albino mice were orally administrated with doses of 50\u00a0mg\/kg and 100\u00a0mg\/kg of body weight (bw) for 5 weeks before the CUMS protocols, respectively. In silico investigation is done with pkCSM software for the ADMET study, and molecular docking is performed on hydroxychavicol with target protein 2ZOQ in Schr\u00f6dinger. HCRF prevented the irregular behaviors acquired in CUMS model, with reduced hypoactivity and sucrose anhedonia. HCRFs of 50 and 100\u00a0mg\/kg bw diminished the upsurges in the level of tumor necrosis factor alpha (TNF\u2010\u03b1) and interleukin\u20101 beta (IL\u20101\u03b2) in the serum associated with stress. HCRF of 100\u00a0mg\/kg bw improved inflammation in the brain by plummeting the malonaldehyde and increasing the glutathione via revering oxidative stress. HCRF exhibited an activity similar to antidepressants and might be a consequence of the anti\u2010inflammatory action. The molecular simulation and pharmacokinetic study ensured a probable mechanistic approach of hydroxychavicol in CUMS\u2010associated depression through inflammatory pathways.<\/jats:p>","DOI":"10.1002\/cbdv.202402842","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T07:51:20Z","timestamp":1743493880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antidepressant\u2010Like Effects of Hydroxychavicol\u2010Enriched <i>Piper betle<\/i> L. Leaf Extract in Chronic Mild Stress\u2013Induced Rodent Models and Possible Mechanism(s) of Action Involved"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7333-3596","authenticated-orcid":false,"given":"Sejuti Ray","family":"Chowdhury","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Health &amp; Medical Sciences Adamas University  Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4796-6016","authenticated-orcid":false,"given":"Sourav","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Health &amp; Medical Sciences Adamas University  Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9334-9919","authenticated-orcid":false,"given":"Shilpa","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Health &amp; Medical Sciences Adamas University  Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7468-1131","authenticated-orcid":false,"given":"Sheikh","family":"Murtuja","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Health &amp; Medical Sciences Adamas University  Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1341-7289","authenticated-orcid":false,"given":"Gourav","family":"Rakshit","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Science and Technology Birla Institute of Technology, Mesra  Ranchi Jharkhand India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8442-801X","authenticated-orcid":false,"given":"Biswajit","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Health &amp; Medical Sciences Adamas University  Kolkata West Bengal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8242-4541","authenticated-orcid":false,"given":"Bhupendra","family":"Prajapati","sequence":"additional","affiliation":[{"name":"S. K. Patel College of Pharmaceutical Education and Research Ganpat University  Mehsana Gujarat India"},{"name":"Centre for Research Impact &amp; Outcome, Chitkara College of Pharmacy Chitkara University  Rajpura Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nemat","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.26599\/SAB.2021.9060001","article-title":"Animal Models of Stress and Stress\u2010Related Neurocircuits: A Comprehensive Review","volume":"1","author":"Ma M.","year":"2021","journal-title":"Stress Brain"},{"issue":"2","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.yhbeh.2007.11.001","article-title":"Long\u2010Term Behavioral and Neuroendocrine Alterations Following Chronic Social Stress in Mice: Implications for Stress\u2010Related Disorders","volume":"53","author":"Sterlemann V.","year":"2008","journal-title":"Hormones and Behavior"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s11010-015-2524-x","article-title":"Reduction of Oxidative Stress by an Ethanolic Extract of Leaves of Piper betle (Paan) Linn. 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