{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:42:58Z","timestamp":1792496578012,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytochemical Analysis"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim of the Study<\/jats:title>\n                    <jats:p>Integrating metabolomics, network pharmacology, and zebrafish depression models, this study explored the pharmacodynamic material basis and potential quality markers (Q\u2010markers) of Yueju Wan (YJW) against depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Chronic unpredictable mild stress (CUMS) was adopted to establish a rat depression model for evaluating the antidepressant efficacy of YJW. UPLC\u2010QTOF\u2010MS\/MS was utilized to characterize the chemical constituents of YJW, and relevant databases were employed to predict its potential therapeutic targets. Metabolomics analysis was performed to screen differential metabolites in serum and urine, followed by pathway enrichment analysis. A compound\u2013target\u2013metabolite\u2013pathway interaction network was constructed to screen core therapeutic targets and candidate pharmacodynamic substances, and RT\u2010qPCR, Western blot, and zebrafish depression models were applied to validate the identified targets and pharmacological effects. Finally, a quantitative detection method for the candidate quality markers was established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One hundred eight chemical components and 105 core targets were characterized and predicted from YJW, respectively. YJW reversed 87 depression\u2010associated differential metabolites. Further integrated analysis together with RT\u2010qPCR and Western blot validation suggested that Alox15 and Cyp19a1 may be involved in the antidepressant\u2010like effects of YJW, possibly through modulation of arachidonic acid metabolism, microglial polarization, and neuroinflammatory responses. Seventeen compounds including \u03b1\u2010cyperone, geniposide, ferulic acid, and atractylodin were verified to exert antidepressant activities via molecular docking and zebrafish models. Ferulic acid, \u03b1\u2010cyperone, geniposide, and atractylodin show satisfactory detectability and are proposed as potential Q\u2010markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides new evidence for the candidate antidepressant pharmacodynamic substances and potential quality markers of YJW and provides a scientific basis for the new drug development and quality control of YJW.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pca.70095","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:21:04Z","timestamp":1792495264000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on the Active Pharmaceutical Substances and Potential Quality Markers of Yueju Wan Antidepressant Based on Metabolomics"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5484-0373","authenticated-orcid":false,"given":"Shilin","family":"Sun","sequence":"first","affiliation":[{"name":"School of Pharmacy Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4266-9752","authenticated-orcid":false,"given":"Haiqin","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Pharmacy Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghai","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Pharmacy Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-9778","authenticated-orcid":false,"given":"Dongxue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-3647","authenticated-orcid":false,"given":"Xiang","family":"Zou","sequence":"additional","affiliation":[{"name":"Engineering Research Center on Natural Antineoplastic Drugs, Ministry of Education Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1562-0053","authenticated-orcid":false,"given":"Zhongyuan","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Harbin University of Commerce  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010publhealth\u2010031912\u2010114409"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/2057150X211043008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj\u20102022\u2010073823"},{"issue":"2","key":"e_1_2_9_5_1","first-page":"119","article-title":"Analysis of Prof. Huang Wenzheng's Experience in Treating Obesity Using Yueju Pills","volume":"38","author":"Wang L.","year":"2019","journal-title":"Journal of Tianjin University of Traditional Chinese Medicine"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.19945\/j.cnki.issn.1006\u20103250.2015.04.026"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70341"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.119031"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2023.115807"},{"issue":"24","key":"e_1_2_9_10_1","first-page":"8353","article-title":"Based on the Correlation Between \u201cSubstance Efficacy\u201d, a Study on the Antidepressant Active Substances of Chaihu in Vinegar South","volume":"55","author":"Li Z.","year":"2024","journal-title":"Chinese Herbal Medicines"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.13748\/j.cnki.issn1007\u20107693.2019.02.011"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112055"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110470"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010019\u20100228\u20106"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac394"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.121137"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.112199"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2025.120597"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.14188\/j.1671\u20108852.2016.03.002"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2020.122100"},{"issue":"5","key":"e_1_2_9_21_1","first-page":"321","article-title":"Chemical Composition Analysis of Atractylodes lancea and Atractylodes chinensis by UPLC\u2010QTOF\u2010MS\/MS","volume":"28","author":"Zhou J.","year":"2020","journal-title":"Pharmaceutical and Clinical Research"},{"issue":"12","key":"e_1_2_9_22_1","first-page":"1","article-title":"Analysis of Chemical Constituents in Suanzaoren Decoction Granules Based on UPLC\u2010Q\u2010TOF\u2010MS\/MS","volume":"27","author":"Liu J. X.","year":"2021","journal-title":"Chinese Journal of Experimental Traditional Medical Formulae"},{"key":"e_1_2_9_23_1","volume-title":"Study on Pharmacodynamic Material Basis for Anti\u2010Inflammatory and Analgesic Effects and Quality Control of Cyperus rotundus","author":"Yu M.","year":"2023"},{"issue":"12","key":"e_1_2_9_24_1","first-page":"1859","article-title":"Analysis of Component Changes of Scutellariae Radix and Gardeniae Fructus in Single and Combined Decoction of Huangqin Qingfei Decoction by UPLC\u2010LTQ\u2010Orbitrap\u2010MS","volume":"32","author":"Liang K.","year":"2021","journal-title":"Traditional Chinese Drug Research and Clinical Pharmacology"},{"key":"e_1_2_9_25_1","volume-title":"Mechanism of Anxiolytic Effect of Gardeniae Fructus Based on Metabolomics and Network Pharmacology","author":"Yuan F. L.","year":"2022"},{"issue":"14","key":"e_1_2_9_26_1","first-page":"1725","article-title":"Identification of Chemical Constituents of Actinidia chinensis Root by UHPLC\u2010Q\u2010TOF\u2010MS\/MS","volume":"31","author":"Chen F. C.","year":"2020","journal-title":"China Pharmacy"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2018.01.023"},{"issue":"7","key":"e_1_2_9_28_1","first-page":"1638","article-title":"Analysis of Chemical Constituents and Blood\u2010Absorbed Components of Gardeniae Fructus\u2010Cyperi Rhizoma Herb Pair Using UPLC\u2010Q\u2010TOF\u2010M","volume":"45","author":"Zhang Y.","year":"2022","journal-title":"Chinese Medicinal Materials"},{"issue":"8","key":"e_1_2_9_29_1","first-page":"54","article-title":"Isolation, Identification and Bioactivity Research of Flavonoids in Cyperi Rhizoma","volume":"34","author":"Wang Y. J.","year":"2018","journal-title":"Shanxi Journal of Traditional Chinese Medicine"},{"issue":"19","key":"e_1_2_9_30_1","first-page":"3927","article-title":"Identification of Blood Constituents and Metabolites of Menthae Haplocalycis Herba in Rats by UHPLC\u2010Q\u2010TOF\u2010MS\/MS","volume":"48","author":"Zhang Y.","year":"2017","journal-title":"Chinese Herbal Medicines"},{"key":"e_1_2_9_31_1","first-page":"1","article-title":"Analysis of Major Chemical Constituents in Alcohol Extract of Atractylodis Rhizoma\u2010Cyperi Rhizoma Herb Pair Based on UHPLC\u2010Q\u2010TOF\u2010MS\/MS and HPLC","author":"Cao Y.","year":"2024","journal-title":"Chinese Pharmaceutical Journal"},{"issue":"14","key":"e_1_2_9_32_1","first-page":"119","article-title":"Potential Pharmacodynamic Substances and Mechanism of Gardeniae Fructus Against Ischemic Stroke Based on HPLC\u2010Q\u2010TOF\u2010MS\/MS and Network Pharmacology","volume":"27","author":"Gao Y.","year":"2021","journal-title":"Chinese Journal of Experimental Traditional Medical Formulae"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.324383"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175979"},{"key":"e_1_2_9_35_1","first-page":"1","article-title":"Advances in Our Understanding of Oxylipins Derived From Arachidonic Acid","volume":"120","author":"Gabbs M.","year":"2015","journal-title":"Prostaglandins & Other Lipid Mediators"},{"key":"e_1_2_9_36_1","first-page":"17","article-title":"The Biosynthesis, Biological Effects, and Analysis of Leukotrienes and Lipoxins","volume":"116","author":"Powell W. S.","year":"2015","journal-title":"Prostaglandins & Other Lipid Mediators"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.06.016"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.12.014"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201020895\u2010z"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201089964\u20100"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2018.1450033"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2019.05.011"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2017.09.019"},{"issue":"1","key":"e_1_2_9_44_1","first-page":"17","article-title":"Separation and Determination of Selected Polyphenols From Medicinal Plants","volume":"57","author":"Hejniak J.","year":"2018","journal-title":"Journal of Chromatographic Science"}],"container-title":["Phytochemical Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pca.70095","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pca.70095","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pca.70095","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:21:10Z","timestamp":1792495270000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/pca.70095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":43,"alternative-id":["10.1002\/pca.70095"],"URL":"https:\/\/doi.org\/10.1002\/pca.70095","archive":["Portico"],"relation":{},"ISSN":["0958-0344","1099-1565"],"issn-type":[{"value":"0958-0344","type":"print"},{"value":"1099-1565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"2026-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"pca.70095"}}