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F. Chou, has been used as a sedative in China and other Asian countries for over a millennium. However, its quality markers (Q\u2010markers) are not completely clear. In this study, Q\u2010markers selected by a metabolic in vivo study combined with network pharmacology are proposed for ZSS quality control. An UHPLC (ultra\u2010high\u2010performance liquid chromatography)\u2010Q\u2010Orbitrap\u2010MS method was developed to identify or tentatively assign 48 components including 21 flavonoid C\u2010<jats:italic>glycosides<\/jats:italic>, 2 flavonoid O\u2010<jats:italic>glycosides<\/jats:italic>, 11 dammarane triterpenoid saponins, 13 alkaloids, and 1 other, using a diagnostic product ion filtering strategy in ZSS. Subsequently, 147 metabolites detected from serum, urine, bile, and feces samples of <jats:italic>para<\/jats:italic>\u2010chlorophenylalanine\u2013induced insomnia rats treated with ZSS aqueous extracts could be linked to their respective parent compounds, including 27 prototypes. Meanwhile, three metabolic networks of flavonoids, saponins, and alkaloids are preliminarily established and potential metabolic pathways are investigated under the insomnia condition. Finally, 12 key bioactive components against insomnia including magnoflorine, caaverine, coclaurine, norisocorydine, genkwanin, juzinrine, apigenin, jujubogenin, kaempferol\u20103\u2010O\u2010<jats:italic>rutinoside<\/jats:italic>, jujuboside A, jujuboside B, and spinosin with the highest degree values in component\u2013target\u2013pathways network were selected as Q\u2010markers for the quality control of ZSS.<\/jats:p>","DOI":"10.1002\/bmc.5530","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T11:38:56Z","timestamp":1666265936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A strategy to explore the quality markers of Ziziphi Spinosae semen by combining metabolic in vivo study with network pharmacology"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2120-4662","authenticated-orcid":false,"given":"Yan","family":"Yan","sequence":"first","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine Shanxi University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Liu","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine Shanxi University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine Shanxi University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine Shanxi University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyun","family":"Shi","sequence":"additional","affiliation":[{"name":"Thermo Fisher Scientific (China), Co., Ltd  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-3364","authenticated-orcid":false,"given":"Xuemei","family":"Qin","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine Shanxi University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0931-8878","authenticated-orcid":false,"given":"Chenhui","family":"Du","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Materia Medica Shanxi University of Chinese Medicine  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pca.2800050208"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2010.03.023"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114336"},{"key":"e_1_2_8_5_1","first-page":"4634","article-title":"Investigation and predictive analysis on Q\u2010marker of Ziziphi Spinosae semen based on human intestinal microbiota transformation","volume":"50","author":"Cui X. 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