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An insomnia model was induced in mice by DL\u20104\u2010chlorophenylalanine (PCPA) and chronic tail clamping. The sedative effect was evaluated by behavioral tests. Serum components from GJPZSS were analyzed by UHPLC\u2010Q\u2010TOF\u2010MS\/MS, and 64 potential targets were identified. The cAMP signaling pathway was enriched as the core pathway by Kyoto Encyclopedia of genes and genomes (KEGG) analysis and was validated by molecular docking. GJPZSS was demonstrated to prolong sleep time, reduce immobility time, increase 5\u2010hydroxytryptamine (5\u2010HT) and gamma\u2010aminobutyric acid (GABA) levels, decrease hypothalamic\u2010pituitary\u2010adrenal (HPA) axis levels, and suppress neuronal death. The reduction of the cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP\u2010response element binding protein (CREB) and brain\u2010derived neurotrophic factor (BDNF) in the brain was also significantly inhibited. It was concluded that the sleep\u2010improving effect of GJPZSS was mediated through the regulation of the HPA axis and the cAMP\/PKA\/CREB\/BDNF signaling pathway.<\/jats:p>","DOI":"10.1002\/mnfr.70327","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:16:50Z","timestamp":1769062610000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery of the Underlying Mechanism of Ginger Juice Processed Ziziphi Spinosae Semen for Its Sedative\u2010Hypnotic Effect on Insomnia Mice via Regulation of HPA Axis and cAMP\/PKA Signaling Pathway"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0300-2828","authenticated-orcid":false,"given":"Lintong","family":"Xie","sequence":"first","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Xue","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizhen","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1345002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.193"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(01)00498-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113030"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111311"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1056"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.5694\/mja13.10718"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00878-9"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118048"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods11152320"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5759"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00076"},{"key":"e_1_2_10_14_1","first-page":"2762","article-title":"Study on Medication Regularity of Grand Master of Traditional Chinese Medicine YAN Zheng\u2010Hua's Ostreae Concha\u2010Containing Prescriptions Based on Data Mining","volume":"39","author":"Wu J. 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