{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:41:49Z","timestamp":1792528909318,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Zhi-Zi Hou-Po Decoction (ZHD) has been widely used in the treatment of depression for centuries. This study aimed to investigate the antidepressant effects of the water extract of ZHD (ZHD-WE) and ethanol extract of ZHD (ZHD-EE) using behavioral despair tests in mice, and to further explore the neuroprotective effects in a PC12 cell injury model induced by corticosterone (CORT). Mice were divided into a control group (normal saline), ZHD-WE groups (4, 8, and 16\u00a0g\u00a0kg<jats:sup>\u22121<\/jats:sup>), ZHD-EE groups (4, 8, and 16\u00a0g\u00a0kg<jats:sup>\u22121<\/jats:sup>) and the fluoxetine group (20\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>). The forced swimming test (FST) and tail suspension test (TST) were used to screen the antidepressant effects of ZHD-WE and ZHD-EE after oral administration for seven consecutive days. The level of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined by ELISA. The MTT, lactate dehydrogenase (LDH) and flow cytometry analysis were performed to elucidate the neuroprotective effect of ZHD-EE on a PC12 cell injury model. Additionally, the mRNA and proteins expression of apoptotic molecules Bax, Bcl-2 and BDNF were detected by RT-PCR and western blot assay. It showed that ZHD-EE at concentrations of 8 and 16\u00a0g\u00a0kg<jats:sup>\u22121<\/jats:sup> significantly decreased the immobility time in the TST and FST, and increased the BDNF levels in the hippocampus. While ZHD-WE at concentrations of 4, 8, and 16\u00a0g\u00a0kg<jats:sup>\u22121<\/jats:sup> had no significant effect on the immobility time in the TST, and only the 16\u00a0g\u00a0kg<jats:sup>\u22121<\/jats:sup> of extract group significantly decreased the immobility time in the FST. <jats:italic>In vitro,<\/jats:italic> the obtained results showed that PC12 cells pre-incubated with ZHD-EE at concentrations of 100 and 400\u00a0\u03bcg\u00a0ml<jats:sup>\u22121<\/jats:sup> improved cell viability, decreased LDH release, and reduced apoptosis rate of PC12 cells. Moreover, ZHD-EE significantly increased the mRNA and proteins expression of Bcl-2 and BDNF, while decreased the mRNA and protein expression of Bax. ZHD-EE significantly improved <jats:ext-link>despair-like behavior<\/jats:ext-link> in mice, and its mechanism may be related to BDNF upregulation in the hippocampus. This study also showed that ZHD-EE had a protective effect on CORT-induced injury in PC12 cells by upregulating the expression of BDNF and restoring Bcl-2\/Bax balance.<\/jats:p>","DOI":"10.3389\/fphar.2022.918776","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T16:17:22Z","timestamp":1657124242000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Potential Anti-Depressive Effects and Mechanisms of Zhi-Zi Hou-Po Decoction Using Behavioral Despair Tests Combined With in Vitro Approaches"],"prefix":"10.3389","volume":"13","author":[{"given":"Yongtao","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoliang","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzheng","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhou","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.2147\/DDDT.S103216","article-title":"Acetogenins from Annona Muricata as Potential Inhibitors of Antiapoptotic Proteins: a Molecular Modeling Study","volume":"10","author":"Antony","year":"2016","journal-title":"Drug Des. 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