{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:27:38Z","timestamp":1760243258784,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2014,6,12]],"date-time":"2014-06-12T00:00:00Z","timestamp":1402531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, the antidepressant-like effects of Morus alba fractions in rats were investigated in the forced swim test (FST). Male Wistar rats (9-week-old) were administered orally the M. alba ethyl acetate (EtOAc 30 and 100 mg\/kg) and M. alba n-butanol fractions (n-BuOH 30 and 100 mg\/kg) every day for 7 consecutive days. On day 7, 1 h after the final administration of the fractions, the rats were exposed to the FST. M. alba EtOAc fraction at the dose of 100 mg\/kg induced a decrease in immobility behavior (p &lt; 0.01) with a concomitant increase in both climbing (p &lt; 0.05) and swimming (p &lt; 0.05) behaviors when compared with the control group, and M. alba EtOAc fraction at the dose of 100 mg\/kg decreased the hypothalamic-pituitary-adrenal (HPA) axis response to the stress, as indicated by an attenuated corticosterone response and decreased c-fos immunoreactivity in the hippocampal and hypothalamic paraventricular nucleus (PVN) region. These findings demonstrated that M. alba EtOAc fraction have beneficial effects on depressive behaviors and restore both altered c-fos expression and HPA activity.<\/jats:p>","DOI":"10.3390\/molecules19067981","type":"journal-article","created":{"date-parts":[[2014,6,12]],"date-time":"2014-06-12T11:14:31Z","timestamp":1402571671000},"page":"7981-7989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Antidepressant-Like Effects of the Ethyl Acetate Soluble Fraction of the Root Bark of Morus alba on the Immobility Behavior of Rats in the Forced Swim Test"],"prefix":"10.3390","volume":"19","author":[{"given":"Dong","family":"Lim","sequence":"first","affiliation":[{"name":"Food Resource Research Center, Korea Food Research Institute, Seongnam 463-746, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3404-6977","authenticated-orcid":false,"given":"Yun","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Group of Food Functionality, Korea Food Research Institute, Seongnam 463-746, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Hae","family":"Park","sequence":"additional","affiliation":[{"name":"Graduate School of Biotechnology and Research Institute of Life Sciences & Resources,  Kyung Hee University, Yongin 446-701, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9438-2817","authenticated-orcid":false,"given":"Nam-In","family":"Baek","sequence":"additional","affiliation":[{"name":"Graduate School of Biotechnology and Research Institute of Life Sciences & Resources,  Kyung Hee University, Yongin 446-701, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daeseok","family":"Han","sequence":"additional","affiliation":[{"name":"Food Resource Research Center, Korea Food Research Institute, Seongnam 463-746, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1001\/archpsyc.62.6.617","article-title":"Prevalence, severity, and comorbidity of 12-month dsm-iv disorders in the national comorbidity survey replication","volume":"62","author":"Kessler","year":"2005","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1001\/jama.286.19.2391","article-title":"From the world health organization. Mental health: New understanding, new hope","volume":"286","author":"Brundtland","year":"2001","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1602\/neurorx.2.4.590","article-title":"Innovative approaches for the development of antidepressant drugs: Current and future strategies","volume":"2","author":"Schechter","year":"2005","journal-title":"NeuroRx"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1001\/archpsyc.1997.01830190015002","article-title":"A molecular and cellular theory of depression","volume":"54","author":"Duman","year":"1997","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"739716","DOI":"10.1155\/2013\/739716","article-title":"Chinese herbal medicine and depression: The research evidence","volume":"2013","author":"Butler","year":"2013","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_6","first-page":"741","article-title":"Limbic-hypothalamic-pituitary-adrenal axis in depression: Literature review","volume":"30","author":"Twardowska","year":"1996","journal-title":"Psychiatr. Pol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.pscychresns.2006.11.002","article-title":"Hpa axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic\/paralimbic regions","volume":"155","author":"Aihara","year":"2007","journal-title":"Psychiatry Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0006-3223(00)01088-X","article-title":"Glucocorticoid receptors in major depression: Relevance to pathophysiology and treatment","volume":"49","author":"Pariante","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.psyneuen.2010.03.007","article-title":"The glucocorticoid receptor: Pivot of depression and of antidepressant treatment?","volume":"36","author":"Anacker","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1192\/bjp.177.5.390","article-title":"Future therapeutic targets in mood disorders: The glucocorticoid receptor","volume":"177","author":"McQuade","year":"2000","journal-title":"Br. J. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0960-0760(00)00023-6","article-title":"Impaired transactivation of the glucocorticoid receptor cloned from the guyanese squirrel monkey","volume":"72","author":"Patel","year":"2000","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.1021\/jf010567e","article-title":"Polyhydroxylated alkaloids isolated from mulberry trees (morusalba l.) and silkworms (bombyx mori l.)","volume":"49","author":"Asano","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1248\/cpb.33.3195","article-title":"Structures of two natural hypotensive diels-alder type adducts, mulberrofurans f and g, from the cultivated mulberry tree (morus lhou koidz.)","volume":"33","author":"Fukai","year":"1985","journal-title":"Chem. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jep.2005.03.013","article-title":"Hypoglycemic effect of egyptian morus alba root bark extract: Effect on diabetes and lipid peroxidation of streptozotocin-induced diabetic rats","volume":"100","author":"Singab","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/BF02976452","article-title":"Immunomodulating activity of a polysaccharide isolated from mori cortex radicis","volume":"23","author":"Kim","year":"2000","journal-title":"Arch. Pharmacal Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"246","DOI":"10.4103\/0253-7613.59921","article-title":"Adaptogenic effect of morus alba on chronic footshock-induced stress in rats","volume":"41","author":"Nade","year":"2009","journal-title":"Indian J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00213-004-2048-7","article-title":"Forced swimming test in mice: A review of antidepressant activity","volume":"177","author":"Chenu","year":"2005","journal-title":"Psychopharmacology (Berl)"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0031-9384(00)00213-4","article-title":"Varying responses to the rat forced-swim test under diurnal and nocturnal conditions","volume":"69","author":"Kelliher","year":"2000","journal-title":"Physiol. Behav."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0031-9384(93)90116-W","article-title":"Physiological correlates of the forced swim test in rats","volume":"54","author":"Abel","year":"1993","journal-title":"Physiol. Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"321","DOI":"10.4196\/kjpp.2013.17.4.321","article-title":"Changes in c-fos expression in the forced swimming test: Common and distinct modulation in rat brain by desipramine and citalopram","volume":"17","author":"Choi","year":"2013","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1046\/j.1472-8206.2003.00160.x","article-title":"Monoamine metabolism changes following the mouse forced swimming test but not the tail suspension test","volume":"17","author":"Renard","year":"2003","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_22","first-page":"146","article-title":"The molecular biology of ru486. Is there a role for antiprogestins in the treatment of breast cancer?","volume":"13","author":"Horwitz","year":"1992","journal-title":"Endocr. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jsbmb.2009.07.005","article-title":"Identification of the functional domain of glucocorticoid receptor involved in ru486 antagonism","volume":"117","author":"Lee","year":"2009","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.psyneuen.2010.01.011","article-title":"Mifepristone decreases depression-like behavior and modulates neuroendocrine and central hypothalamic-pituitary-adrenocortical axis responsiveness to stress","volume":"35","author":"Wulsin","year":"2010","journal-title":"Psychoneuroendocrinology"},{"key":"ref_25","first-page":"269","article-title":"Brain corticosteroid receptor balance in health and disease","volume":"19","author":"Vreugdenhil","year":"1998","journal-title":"Endocr. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1159\/000126180","article-title":"Antidepressants increase glucocorticoid and mineralocorticoid receptor mrna expression in rat hippocampus in vivo","volume":"55","author":"Seckl","year":"1992","journal-title":"Neuroendocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.psyneuen.2006.12.013","article-title":"Cognitive impairment associated to hpa axis hyperactivity after maternal separation in rats","volume":"32","author":"Aisa","year":"2007","journal-title":"Psychoneuroendocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbr.2012.08.028","article-title":"Antidepressant-like effects of cortex mori radicis extract via bidirectional phosphorylation of glucocorticoid receptors in the hippocampus","volume":"236","author":"Lee","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/sj.npp.1300402","article-title":"Reduced immobility in the forced swim test in mice with a targeted deletion of the leukemia inhibitory factor (lif) gene","volume":"29","author":"Pechnick","year":"2004","journal-title":"Neuropsychopharmacology"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/6\/7981\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:12:23Z","timestamp":1760217143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/6\/7981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,12]]},"references-count":29,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2014,6]]}},"alternative-id":["molecules19067981"],"URL":"https:\/\/doi.org\/10.3390\/molecules19067981","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2014,6,12]]}}}