{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:57:01Z","timestamp":1790834221770,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271066"],"award-info":[{"award-number":["32271066"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471532"],"award-info":[{"award-number":["82471532"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["23QA1408300"],"award-info":[{"award-number":["23QA1408300"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["[2023]24"],"award-info":[{"award-number":["[2023]24"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Aims<\/jats:title>\n Compound Ciwujia Granules (CWJ) have shown antidepressant\u2010like effects, but the neural and molecular mechanisms underlying these effects remain unclear. This study aimed to investigate the mechanisms by which CWJ ameliorates\u00a0anxiety\u2010 and depression\u2010like behaviors.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A 6\u2010week chronic unpredictable mild stress (CUMS) model was established in rats, and behavioral tests were performed to assess the antidepressant\u2010like effects of CWJ. Resting\u2010state functional magnetic resonance imaging (rs\u2010fMRI), in\u00a0vivo fiber photometry, and chemogenetic manipulation were used to identify the brain region and neuronal population involved in the effects of CWJ. Transcriptomic analysis combined with network pharmacology was used to predict\u00a0candidate molecular pathways, which were further validated by quantitative real\u2010time polymerase chain reaction, immunofluorescence, western blotting, and pharmacological interventions.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n CWJ increased the open\u2010arm ratio in the EPM, reduced FST immobility, and lowered serum corticosterone (CORT) levels in CUMS rats. Convergent rs\u2010fMRI, c\u2010Fos immunostaining, and fiber photometry identified that the dorsomedial prefrontal cortex (dmPFC) was a key brain region involved in the antidepressant\u2010like effects of CWJ. CWJ increased glutamatergic neuronal activity and reduced neuroinflammatory responses associated with TNF\u2010related inflammatory signaling in the dmPFC. Moreover, pharmacological activation of TNF\u2010related inflammatory signaling partially attenuated the behavioral benefits of CWJ, supporting the involvement of \u00a0TNF\u2010related inflammatory signaling in mediating its antidepressant effects.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings suggest\u00a0that CWJ attenuated CUMS\u2010induced anxiety\u2010 and depression\u2010like behaviors by restoring dmPFC glutamatergic neuronal activity and suppressing TNF\u2010related neuroinflammation in the dmPFC.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cns.71178","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:54:52Z","timestamp":1790830492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Compound Ciwujia Granules Attenuate Stress\u2010Induced Anxiety\u2010 and Depression\u2010Like Behaviors via Inhibition of\n TNF<\/scp>\n \u2010\u03b1\u2010Associated Neuroinflammation in the\n dmPFC<\/scp>"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2378-5124","authenticated-orcid":false,"given":"Fei","family":"Tian","sequence":"first","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine Shanghai China"},{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8211-3823","authenticated-orcid":false,"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyu","family":"Dai","sequence":"additional","affiliation":[{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihan","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine Shanghai China"},{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Liao","sequence":"additional","affiliation":[{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6598-5117","authenticated-orcid":false,"given":"Yingdan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gong","sequence":"additional","affiliation":[{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanying","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Shanghai Institute of Traditional Chinese Medicine for Mental Health Shanghai Mental Health Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-7664","authenticated-orcid":false,"given":"Dongdong","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Shanghai Institute of Traditional Chinese Medicine for Mental Health Shanghai Mental Health Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4319-5314","authenticated-orcid":false,"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai University of Traditional Chinese Medicine Shanghai China"},{"name":"Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Shanghai Institute of Traditional Chinese Medicine for Mental Health Shanghai Mental Health Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"1","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-023-00454-1","article-title":"Major depressive disorder","volume":"9","author":"Marx W.","year":"2023","journal-title":"Nature Reviews Disease Primers"},{"issue":"10128","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/S0140-6736(17)32802-7","article-title":"Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults With Major Depressive Disorder: A Systematic Review and Network Meta\u2010Analysis","volume":"391","author":"Cipriani A.","year":"2018","journal-title":"Lancet"},{"issue":"10161","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi G. 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Antidepressants and the Current and Future Pharmacological Management of Depression","volume":"2","author":"Penn E.","year":"2012","journal-title":"Therapeutic Advances in Psychopharmacology"},{"key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.bbi.2024.09.013","article-title":"Dissecting Depression Symptoms: Multi\u2010Omics Clustering Uncovers Immune\u2010Related Subgroups and Cell\u2010Type Specific Dysregulation","volume":"123","author":"Hagenberg J.","year":"2025","journal-title":"Brain, Behavior, and Immunity"},{"issue":"4","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","DOI":"10.1136\/gpsych-2022-100844","article-title":"TNF\u2010\u03b1, IL\u20106 and hsCRP in Patients With Melancholic, Atypical and Anxious Depression: An Antibody Array Analysis Related to Somatic Symptoms","volume":"35","author":"Liu H.","year":"2022","journal-title":"General Psychiatry"},{"issue":"3","key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1001\/jamapsychiatry.2014.2427","article-title":"Role of Translocator Protein Density, a Marker of Neuroinflammation, in the Brain During Major Depressive Episodes","volume":"72","author":"Setiawan E.","year":"2015","journal-title":"JAMA Psychiatry"},{"issue":"9","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1177\/0269881117711708","article-title":"Anti\u2010Inflammatory Treatment for Major Depressive Disorder: Implications for Patients With an Elevated Immune Profile and Non\u2010Responders to Standard Antidepressant Therapy","volume":"31","author":"Feltes P. 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New Insights Into the Effects of \n Acanthopanax senticosus\n Harms on Nervous System Through Cerebral Metabolomics Analysis","volume":"156","author":"Zhang S.","year":"2014","journal-title":"Journal of Ethnopharmacology"},{"issue":"1","key":"e_1_2_13_21_1","doi-asserted-by":"crossref","first-page":"E61","DOI":"10.1503\/jpn.220147","article-title":"Sex\u2010Specific Transcriptional Signatures in the Medial Prefrontal Cortex Underlying Sexually Dimorphic Behavioural Responses to Stress in Rats","volume":"48","author":"Zhang Y.\u2010D.","year":"2023","journal-title":"Journal of Psychiatry and Neuroscience"},{"issue":"1","key":"e_1_2_13_22_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-42814-1","article-title":"Stress\u2010Induced Red Nucleus Attenuation Induces Anxiety\u2010Like Behavior and Lymph Node CCL5 Secretion","volume":"14","author":"Shi D.\u2010D.","year":"2023","journal-title":"Nature Communications"},{"issue":"2","key":"e_1_2_13_23_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1192\/bjp.bp.115.180653","article-title":"Cortisol as a Predictor of Psychological Therapy Response in Depressive Disorders: Systematic Review and Meta\u2010Analysis","volume":"210","author":"Fischer S.","year":"2017","journal-title":"British Journal of Psychiatry"},{"issue":"1","key":"e_1_2_13_24_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41398-021-01733-9","article-title":"Chronic Cortisol Differentially Impacts Stem Cell\u2010Derived Astrocytes From Major Depressive Disorder Patients","volume":"11","author":"Heard K. 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