{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:52:49Z","timestamp":1791859969311,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Major depressive disorder (MDD) is a prevalent mental illness with a significant disease burden. It is characterized by immune\u2010inflammatory dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This ex vivo study assessed curcumin's immunomodulatory effects in 18 MDD patients and 18 healthy controls (HC). Whole blood samples underwent LPS\u2010 and PHA\u2010stimulation to evaluate immune sensitization with curcumin treatment at concentrations of 2, 20, and 200\u00a0ng\/mL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MDD patients exhibited marked activation of the immune\u2010inflammatory response system (IRS), M1 macrophages, T helper (Th) 1, growth factors, and chemokine profiles, whereas M2, Th2, and the compensatory immunoregulatory system (CIRS) were less activated, confirming IRS sensitization in MDD. Partial regression analysis confirmed positive correlations between immune biomarkers (e.g., IL\u20101\u03b2) and depression severity scores. In patients with MDD, curcumin selectively and significantly downregulated the overactivated IRS, M1, Th1, and chemokine profiles. Notably, curcumin significantly decreased pro\u2010inflammatory chemokines, such as CCL11, CXCL10, and CCL27, and exhibited inhibitory effects on key inflammatory factors, including TNF\u2010\u03b1. Although curcumin did not fully normalize the IRS profiles or significantly affect M2, Th2, or CIRS profiles, its specific inhibition of core inflammatory pathways clearly demonstrates its ability to selectively modulate aberrant immune responses in MDD. Paradoxically, in HC, curcumin showed mild immune\u2010stimulating effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate that curcumin exerts selective anti\u2010inflammatory effects by effectively targeting and suppressing overactivated core inflammatory pathways (e.g., IRS\/M1\/Th1 and related chemokines) in MDD patients, thereby partially restoring immune homeostasis. This supports the potential role of curcumin as an adjunctive therapeutic strategy for MDD. However, as these findings are derived from an ex vivo model, further in vivo studies are required before clinical recommendations can be made.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71672","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:15:51Z","timestamp":1786522551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Selective Anti\u2010Inflammatory Actions of Curcumin on Cytokine Pathways in Major Depressive Disorder"],"prefix":"10.1002","volume":"16","author":[{"given":"Tangcong","family":"Chen","sequence":"first","affiliation":[{"name":"Sichuan Provincial Center for Mental Health Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China  Chengdu China"},{"name":"Key Laboratory of Psychosomatic Medicine Chinese Academy of Medical Sciences  Chengdu 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