{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T19:51:44Z","timestamp":1792353104385,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Major depressive disorder (MDD) is a severe mental disorder associated with high rates of morbidity and mortality. Current first\u2010line pharmacotherapies for MDD are based on enhancement of monoaminergic neurotransmission, but these antidepressants are still insufficient and produce significant side\u2010effects. Consequently, the development of novel antidepressants and therapeutic targets is desired. Engeletin, a natural <jats:italic>Smilax glabra rhizomilax<\/jats:italic> derivative, is a compound with proven efficacy in treating ischemic stroke, yet its therapeutic effects and mechanisms for depression remain unexplored. The effects of engeletin were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Engeletin was also investigated in the chronic restraint stress (CRS) mouse model of depression with fluoxetine (FLX) as the positive control. Changes in prefrontal cortex (PFC) spine density, synaptic plasticity\u2010linked protein expressions and the brain\u2010derived neurotrophic factor (BDNF)\u2010tyrosine kinase B (TrkB)\u2010 mammalian target of rapamycin complex 1 (mTORC1) signalling pathway after chronic stress and engeletin treatment were then investigated. The TrkB and mTORC1 selective inhibitors, ANA\u201012 and rapamycin, respectively, were utilized to assess the engeletin's antidepressive mechanisms. Our data shows that engeletin exhibited antidepressant\u2010like activity in the FST and TST in mice without affecting locomotor activity. Furthermore, it exhibited efficiency against the depression of CRS model. Moreover, it enhanced the BDNF\u2010TrkB\u2010mTORC1 pathway in the PFC during CRS and altered the reduction in dendritic spine density and levels of synaptic plasticity\u2010linked protein induced by CRS. In conclusion, engeletin has antidepressant activity via activation of the BDNF\u2010TrkB\u2010mTORC1 signalling pathway and upregulation of PFC synaptic plasticity.<\/jats:p>","DOI":"10.1111\/jcmm.17975","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T17:39:35Z","timestamp":1696613975000},"page":"3928-3938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Engeletin alleviates depression\u2010like phenotype by increasing synaptic plasticity via the BDNF\u2010TrkB\u2010mTORC1 signalling pathway"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6427-7250","authenticated-orcid":false,"given":"Yangyang","family":"Xu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University  Yantai P. 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