{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:09:35Z","timestamp":1789168175356,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["Food Science &amp; Nutrition"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent joint inflammation and progressive joint destruction, leading to pain, disability, and reduced quality of life. Interleukin\u20106 is a key pro\u2010inflammatory cytokine that plays a central role in the pathogenesis of rheumatoid arthritis by activating downstream inflammatory signaling pathways. Dysregulation of the interleukin\u20106\u2010mediated signaling cascade, particularly the signal transducer and activator of transcription 3 pathway, contributes to sustained inflammation and disease progression, highlighting this axis as an important therapeutic target. Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and destruction, with interleukin\u20106 (IL\u20106) playing a central role in its pathogenesis by driving inflammatory responses. Targeting the IL\u20106\/signal transducer and activator of transcription 3 (STAT3) pathway has emerged as a promising therapeutic approach for RA. This study investigates the inhibitory effects and underlying mechanisms of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010trans\u2010hibiscusamide (NHA) and its derivative 4\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010(\n                    <jats:italic>E<\/jats:italic>\n                    )\u2010feruloyl\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(\n                    <jats:italic>E<\/jats:italic>\n                    )\u2010hibiscusamide (HAD) on the IL\u20106\/STAT3 signaling axis. Using a phosphorylated STAT3 luciferase reporter assay, NHA and HAD significantly reduced IL\u20106\u2010induced luciferase activity. They also downregulated IL\u20106\u2010induced gene expression, inhibited STAT3 nuclear translocation and phosphorylation of signaling molecules, and suppressed IL\u20106\/interleukin\u20106 receptor binding. In a collagen\u2010induced arthritis mouse model, both compounds alleviated arthritis symptoms, decreased serum levels of anti\u2010type II collagen immunoglobulin G and interleukin\u201017A, and downregulated T helper 17\u2010specific genes in the spleen. Furthermore, in\u00a0vitro experiments demonstrated that NHA and HAD inhibited the differentiation of na\u00efve CD4\u2010positive T cells into T helper 17 cells. These findings suggest that NHA and HAD effectively modulate interleukin\u20106\u2013mediated inflammatory signaling and may serve as potential therapeutic candidates for the management of rheumatoid arthritis.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71601","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:31:33Z","timestamp":1773030693000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of IL\u20106\/STAT3 Signaling by N\u2010Trans\u2010Hibiscusamide and Its Derivative in a Mouse Model of Collagen\u2010Induced Arthritis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-6766","authenticated-orcid":false,"given":"Hyung Jin","family":"Lim","sequence":"first","affiliation":[{"name":"Scripps Korea Antibody Institute  Chuncheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon 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Jae","family":"Park","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Jeongeup Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Woong","family":"Lee","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Jeongeup Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Functional Food Research Korea Food Research Institute  Wanju Korea"},{"name":"Department of Food Biotechnology University of Science and Technology (UST)  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Functional Food Research Korea Food Research Institute  Wanju 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