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Considering the disadvantages of decoction, our research group prepared ZZHPD into Zhi\u2010Zi\u2010Hou\u2010Po Granule (ZZHPG). However, the chemical composition and mechanism of ZZHPG for the treatment of depression\u2013anxiety comorbidity remain unclear. In this study, the UHPLC\u2010Q\u2010TOF\u2010MS technology was applied to investigate the chemical constituents in ZZHPG, and network pharmacology was used to reveal the mechanism of ZZHPG. A total of 92 compounds were identified in ZZHPG. The network pharmacological analysis showed that 92 compounds regulated 132 pathways through 90 targets, among which 17 compounds maybe the material basis of ZZHPG for the treatment of depression\u2013anxiety comorbidity, and osthole, obovatol, and naringenin may be the main pharmacodynamic components. Further research indicated that the mechanism of ZZHPG in treating depression\u2013anxiety comorbidity may be related to the inhibition of nervous system disorders, activation of GABA receptors, anti\u2010inflammation, and reduction of oxidative stress. The molecular docking results showed that osthole, obovatol, and naringenin exhibited strong binding affinity with the core targets AKT1, ALB, TNF, EGFR, ESR1, and GSK3B. This research laid foundation for clinical application of ZZHPG and provided new ideas for the study of other TCM prescriptions.<\/jats:p>","DOI":"10.1002\/bmc.70338","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T03:54:42Z","timestamp":1766721282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated UHPLC\u2010Q\u2010TOF\u2010MS Technology and Network Pharmacology Exploring the Pharmacodynamic Material Basis and Mechanism of Zhi\u2010Zi\u2010Hou\u2010Po Granule for Treatment of Depression\u2013Anxiety Comorbidity"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3945-8455","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"},{"name":"School of Pharmacy Yanbian University  Yanji Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Guan","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"},{"name":"School of Pharmacy Yanbian University  Yanji Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"},{"name":"School of Pharmacy Yanbian University  Yanji Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"},{"name":"School of Pharmacy Yanbian University  Yanji Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengyu","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2999-2344","authenticated-orcid":false,"given":"Lele","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Pharmacy Yanbian University  Yanji Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0212-0121","authenticated-orcid":false,"given":"Heyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Jilin Medical University  Jilin Jilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.641909"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2016.04.014"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-01940-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.9734\/jpri\/2021\/v33i47B33168"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1037\/ccp0000865"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145707007924"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010025\u201004195\u20108"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.111.2.244"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2024.105811"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.03.031"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/life13010099"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27217313"},{"issue":"8","key":"e_1_2_8_14_1","article-title":"Unraveling the Tapestry of Depression: a Cross\u2010Sectional Study","volume":"16","author":"Gandhi R.","year":"2024","journal-title":"Cureus Journal of Medical Science"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crfs.2022.11.013"},{"issue":"5","key":"e_1_2_8_16_1","first-page":"373","article-title":"Factors of Risk for Suicidal Behavior Associated With Depressive Disorders and Anxiety","volume":"37","author":"Garcia E. 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