{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T01:27:45Z","timestamp":1776734865257,"version":"3.51.2"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T00:00:00Z","timestamp":1650067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["81173530"],"award-info":[{"award-number":["81173530"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["17JCZDJC33200"],"award-info":[{"award-number":["17JCZDJC33200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["TJYY1705"],"award-info":[{"award-number":["TJYY1705"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tianjin Research Program of Applied Basic and Cutting-Edge Technology","award":["81173530"],"award-info":[{"award-number":["81173530"]}]},{"name":"Tianjin Research Program of Applied Basic and Cutting-Edge Technology","award":["17JCZDJC33200"],"award-info":[{"award-number":["17JCZDJC33200"]}]},{"name":"Tianjin Research Program of Applied Basic and Cutting-Edge Technology","award":["TJYY1705"],"award-info":[{"award-number":["TJYY1705"]}]},{"name":"Tianjin Hospital Foundation","award":["81173530"],"award-info":[{"award-number":["81173530"]}]},{"name":"Tianjin Hospital Foundation","award":["17JCZDJC33200"],"award-info":[{"award-number":["17JCZDJC33200"]}]},{"name":"Tianjin Hospital Foundation","award":["TJYY1705"],"award-info":[{"award-number":["TJYY1705"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2022,4,16]]},"abstract":"<jats:p>Context. Ziziphi Spinosae Semen (ZSS) is a well-known Chinese herbal medicine used in the treatment of depression and anxiety in China. ZSS contains several active components, such as alkaloids, saponins, and flavonoids. Objective. This study aimed to explore the synergistic effect of alkaloids and saponins from ZSS in alleviating depression in a mouse model. Materials and Methods. Modeling depression with chronic unpredictable stimuli. Pharmacodynamic methods (tail suspension test and forced swimming test) were used to evaluate the antidepressant effects of alkaloids, saponins, and combinations thereof from ZSS. The mechanisms underlying the effect were examined by measuring the levels of monoamine neurotransmitters in the hippocampus and frontal cortex of mice. Results. Compared with the model group, alkaloids therapy (AZSS), saponins therapy (SZSS), and combination therapy significantly reduced the immobility time in behavioral tests (<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>P<\/a:mi>\n                        <a:mo>&lt;<\/a:mo>\n                        <a:mn>0.05<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>). The contents of noradrenaline (NE), dopamine (DA), and serotonin (5-HT) in the hippocampus and frontal cortex of depressed mice were increased in the drug treatment groups, especially in the combination group, which increased by 14.65%, 87.72%, 33.44%, 25.64%, 25.39%, and 70.78%, respectively. Several groups showed better results (<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>P<\/c:mi>\n                        <c:mo>&lt;<\/c:mo>\n                        <c:mn>0.05<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>), especially the combination of alkaloids and saponins. Discussion and Conclusion. The saponins and alkaloids from ZSS exhibited a synergistic effect in improving the behavior of depressed mice. More importantly, the combination of alkaloids (15\u2009mg\u00b7kg\u22121) and saponins (110\u2009mg\u00b7kg\u22121) was effective in alleviating depression in mice, especially in terms of changing the level of DA in the hippocampus.<\/jats:p>","DOI":"10.1155\/2022\/5755980","type":"journal-article","created":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T18:35:06Z","timestamp":1650134106000},"page":"1-9","source":"Crossref","is-referenced-by-count":4,"title":["The Synergistic Antidepressant Effect: Compatibility of Alkaloids with Saponins from Ziziphi Spinosae Semen"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5970-0293","authenticated-orcid":true,"given":"Lu","family":"Li","sequence":"first","affiliation":[{"name":"Tianjin Hospital, Tianjin 300211, China"},{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5239-4361","authenticated-orcid":true,"given":"Wei","family":"Song","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0789-4030","authenticated-orcid":true,"given":"Qianqian","family":"Chang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5148-993X","authenticated-orcid":true,"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6344-0324","authenticated-orcid":true,"given":"Demin","family":"Fang","sequence":"additional","affiliation":[{"name":"Tianjin Hospital, Tianjin 300211, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2515-0841","authenticated-orcid":true,"given":"Wei","family":"Qiao","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004188.pub3"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2018.08.013"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31948-2"},{"key":"4","first-page":"667","article-title":"Antidepressants in use in clinical practice","volume":"29","author":"A. Mark","year":"2017","journal-title":"Psychiatria Danubina"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x1304150831122734"},{"key":"6","first-page":"5180","article-title":"Chinese herbal medicine for the treatment of depression: applications, efficacies and mechanisms","volume":"35","author":"Y. Y. Wang","year":"2017","journal-title":"Current Pharmaceutical Design"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5861821"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2010.03.023"},{"key":"9","first-page":"7","article-title":"Study on the compatibility of anti-depressant active ingredients in Ziziphi Spinosae Semen","volume":"23","author":"Y. Yang","year":"2012","journal-title":"LISHIZHEN Medicine And Materia Research."},{"key":"10","doi-asserted-by":"crossref","first-page":"634","DOI":"10.5567\/pharmacologia.2013.634.640","article-title":"Antidepressant-like effects of total alkaloids from semen zizyphi sponosae in mice models of depression","volume":"4","author":"Y. Sun","year":"2013","journal-title":"Pharmacologia"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666190402105803"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1097\/01376517-200004000-00005"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2012.02.026"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.06.044"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(69)90387-x"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1970.tb10373.x"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-017-1749-5"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2016.08.002"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1002\/0471141755.ph0565s61"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2019.112053"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x1304150831120428"}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2022\/5755980.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2022\/5755980.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2022\/5755980.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T18:35:19Z","timestamp":1650134119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ecam\/2022\/5755980\/"}},"subtitle":[],"editor":[{"given":"Md. Areeful","family":"Haque","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,4,16]]},"references-count":21,"alternative-id":["5755980","5755980"],"URL":"https:\/\/doi.org\/10.1155\/2022\/5755980","relation":{},"ISSN":["1741-4288","1741-427X"],"issn-type":[{"value":"1741-4288","type":"electronic"},{"value":"1741-427X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4,16]]}}}