{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:10Z","timestamp":1786977910828,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) remains a significant clinical challenge due to the limited efficacy and adverse effects associated with conventional treatments. Danggui buxue decoction (DBD), renowned for its qi\u2010tonifying, blood\u2010nourishing, and anti\u2010inflammatory properties, has shown promising potential in the management of RA. This study investigates the mechanisms of DBD in RA through bioinformatics and experimental analyses, providing a scientific foundation for its clinical application and further development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The chemical components and blood\u2010absorbed components of DBD were identified using UPLC\u2010MS\/MS. Bioinformatics approaches were applied to identify differentially expressed genes (DEGs) between RA patients and healthy individuals, and to predict potential drug targets and signaling pathways associated with the blood\u2010absorbed components of DBD. Collagen\u2010induced arthritis (CIA) rat models and tumor necrosis factor (TNF)\u2010\u03b1\u2010stimulated human rheumatoid arthritis fibroblast\u2010like synoviocyte (RA\u2010FLS) models were established to evaluate the therapeutic effects of DBD on RA. Serum metabolomics analysis was performed to identify differential metabolites and key metabolic pathways associated with the therapeutic effects of DBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 83 chemical components and 34 blood\u2010absorbed components were identified in DBD. Bioinformatics analysis highlighted the NF\u2010\u03baB signaling pathway as a central regulator of RA\u2010related inflammation, requiring further mechanism exploration. Experimental findings demonstrated that DBD significantly reduced the expression of inflammatory cytokines\u2010IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1\u2010in both RA\u2010FLS cells and serum from CIA rats. Furthermore, DBD inhibited RA\u2010FLS cell proliferation and migration while inducing apoptosis. DBD treatment alleviated paw swelling, reduced arthritis scores, and decreased spleen and thymus indices. Histopathological examination (HE) staining showed decreased inflammatory cell infiltration, and Micro\u2010CT results revealed notable mitigation of bone destruction. Metabolomic analysis identified 34 differential metabolites and 4 significant metabolic pathways (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Moreover, DBD significantly downregulated the expression of phosphorylated proteins in both RA\u2010FLS cells and synovial tissue of rats involved in the NF\u2010\u03baB signaling pathway, including p\u2010I\u03baB\u03b1, p\u2010p65, and p\u2010IKK\u03b1, and suppressing NLRP3 protein and mRNA expression of I\u03baB\u03b1, p65, and IKK\u03b1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DBD effectively alleviates RA symptoms by reducing inflammation and inhibiting the activation of the NF\u2010\u03baB signaling pathway through its multi\u2010component and multi\u2010target characteristics. This study provides valuable insights into the molecular mechanisms underlying the anti\u2010RA effects of DBD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70259","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T10:45:13Z","timestamp":1758019513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integration of Bioinformatics, Serum Pharmacochemistry, and Metabolomics to Reveal the Mechanisms of Danggui Buxue Decoction in Anti\u2010Rheumatoid Arthritis Through Inflammation and NF\u2010\u03baB Signaling Pathway Regulation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0953-1871","authenticated-orcid":false,"given":"Lianyun","family":"Du","sequence":"first","affiliation":[{"name":"Jilin Ginseng Academy Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zhai","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixiu","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Tang","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiyue","family":"Qiu","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-7715","authenticated-orcid":false,"given":"Enpeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3798-0825","authenticated-orcid":false,"given":"Zhi","family":"Pan","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.782"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109367"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154140"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.696802"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115325"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6187695"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.127"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6509"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.967164"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.10.010"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5379"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1242318"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-022-2642-0"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114699"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2023.2230753"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.117910"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118713"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202100037"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2024.108775"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2022.981173"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.12.012"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001651"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/pca.3216"},{"key":"e_1_2_11_25_1","first-page":"1","article-title":"Comparative Study on Chemical Constituents of Ginseng Flowers With Four Consecutive Cultivation Age","volume":"2023","author":"Du L. 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