{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T23:01:25Z","timestamp":1780700485232,"version":"3.54.1"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by dysregulated inflammation and intestinal microbiota-gut-joint axis dysfunction. While triptolide, a natural immunosuppressive compound, exhibits anti-RA activity, its mechanism linking gut microbiota modulation, intestinal barrier repair, and inflammatory signaling remains unclear. This study aimed to investigate whether triptolide alleviates adjuvant-induced arthritis (AIA) in mice by regulating the gut microbiota-intestinal barrier-toll-like receptor 4 (TLR4)\/nuclear factor-\u03baB (NF-\u03baB) axis. The anti-inflammatory effect of triptolide was assessed using lipopolysaccharide (LPS)-induced RAW 264.7\u202fcells and primary peritoneal macrophages. The anti-RA efficacy was investigated in AIA mice through detecting inflammatory factors, intestinal barrier integrity and gut microbiota. The results showed that triptolide decreased inflammatory factors in both RAW 264.7\u202fcells and primary peritoneal macrophages. Meanwhile, triptolide dose-dependently reduced AI scores and paw swelling in AIA mice (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05 vs. AIA group), along with restored intestinal barrier integrity by upregulating ZO-1 and Occludin (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.05 vs. AIA group) and modulated gut microbiota. Mechanistically, triptolide inhibited TLR4\/NF-\u03baB activation, reducing downstream pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (TNF-\u03b1)). In sum, these findings reveal that triptolide alleviates AIA by modulating the gut microbiota, repairing the intestinal barrier, and suppressing TLR4\/NF-\u03baB signaling. This highlights a novel \u201cmicrobiota-gut-joint\u201d regulatory mechanism of triptolide, supporting its potential as a therapeutic agent targeting RA\u2019s multifactorial pathogenesis.\n                  <\/jats:p>","DOI":"10.1515\/biol-2025-1290","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T22:15:40Z","timestamp":1780697740000},"source":"Crossref","is-referenced-by-count":0,"title":["Triptolide alleviates rheumatoid arthritis via modulating gut microbiota\u00a0\u2013\u00a0intestinal barrier\u00a0\u2013\u00a0TLR4\/NF-\u03baB axis"],"prefix":"10.1515","volume":"21","author":[{"given":"Xuekang","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Orthopaedics , The Second Affiliated Hospital of Jiaxing University , Jiaxing , 314000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyuan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics , The Second Affiliated Hospital of Jiaxing University , Jiaxing , 314000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3106-9225","authenticated-orcid":false,"given":"Jiaqi","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics , The Second Affiliated Hospital of Jiaxing University , Jiaxing , 314000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huigen","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics , The Second Affiliated Hospital of Jiaxing University , Jiaxing , 314000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics , The Second Affiliated Hospital of Jiaxing University , Jiaxing , 314000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"2026060522080026870_j_biol-2025-1290_ref_001","doi-asserted-by":"crossref","unstructured":"Nguyen, H, Ruyssen-Witrand, A, Gandjbakhch, F, Constantin, A, Foltz, V, Cantagrel, A. Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis. Rheumatol 2014;53:2110\u20138. https:\/\/doi.org\/10.1093\/rheumatology\/keu217.","DOI":"10.1093\/rheumatology\/keu217"},{"key":"2026060522080026870_j_biol-2025-1290_ref_002","doi-asserted-by":"crossref","unstructured":"Soo, J, Eldeiry, D, Katz, S. Prevalence of rheumatoid arthritis in edmonton and northern alberta. Clin Rheumatol 2021;40:1245\u20138. https:\/\/doi.org\/10.1007\/s10067-020-05352-5.","DOI":"10.1007\/s10067-020-05352-5"},{"key":"2026060522080026870_j_biol-2025-1290_ref_003","doi-asserted-by":"crossref","unstructured":"Kapoor, B, Gulati, M. Gut microbiome and rheumatoid arthritis: revisiting the gut-joint axis. Int Immunopharmacol 2025;165:115503. https:\/\/doi.org\/10.1016\/j.intimp.2025.115503.","DOI":"10.1016\/j.intimp.2025.115503"},{"key":"2026060522080026870_j_biol-2025-1290_ref_004","doi-asserted-by":"crossref","unstructured":"Meisinger, C, Freuer, D. Rheumatoid arthritis and inflammatory bowel disease: a bidirectional two-sample mendelian randomization study. Semin Arthritis Rheum 2022;55:151992. https:\/\/doi.org\/10.1016\/j.semarthrit.2022.151992.","DOI":"10.1016\/j.semarthrit.2022.151992"},{"key":"2026060522080026870_j_biol-2025-1290_ref_005","doi-asserted-by":"crossref","unstructured":"Kitamura, K, Shionoya, H, Suzuki, S, Fukai, R, Uda, S, Abe, C, et al.. Oral and intestinal bacterial substances associated with disease activities in patients with rheumatoid arthritis: a cross-sectional clinical study. 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J\u00a0Immunol Res 2017;2017:1\u201313. https:\/\/doi.org\/10.1155\/2017\/4835189.","DOI":"10.1155\/2017\/4835189"},{"key":"2026060522080026870_j_biol-2025-1290_ref_008","doi-asserted-by":"crossref","unstructured":"Chen, J, Wright, K, Davis, JM, Jeraldo, P, Marietta, EV, Murray, J, et al.. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med 2016;8:43. https:\/\/doi.org\/10.1186\/s13073-016-0299-7.","DOI":"10.1186\/s13073-016-0299-7"},{"key":"2026060522080026870_j_biol-2025-1290_ref_009","doi-asserted-by":"crossref","unstructured":"Scher, JU, Sczesnak, A, Longman, RS, Segata, N, Ubeda, C, Bielski, C, et al.. 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