{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:35:10Z","timestamp":1776926110196,"version":"3.51.2"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA).\n                      <jats:italic>Tripterygium wilfordii Hook.f. [Celastraceae]<\/jats:italic>\n                      glycosides (TWG) are used in RA treatment, but their dose-response relationship and involvement of the gut-lung axis in RA-ILD remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Collagen-induced arthritis (CIA) was established in Wistar rats. Animals were assigned to normal control (NC), model, TWG-L (9\u00a0mg\/kg), TWG-M (45\u00a0mg\/kg), TWG-H (90\u00a0mg\/kg), and prednisolone (Pred, 5\u00a0mg\/kg) groups. Treatments were administered by oral gavage from day 15 to day 42, and animals were sacrificed on day 43. Joint and lung pathology was assessed histologically. Fecal microbiota composition was analyzed by 16S rRNA gene sequencing, and microbial functional profiles were predicted using PICRUSt2. RT-qPCR was used to quantify IL-6 and TNF-\u03b1 mRNA expression in joint and lung tissues, while Western blot analysis was used to detect TGF-\u03b21 and \u03b1-SMA protein expression in lung tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TWG ameliorated both arthritis severity and pulmonary injury in a dose-dependent manner, with the strongest effects observed in the TWG-H group, showing efficacy comparable to Pred group. Histopathological analysis showed marked improvement in synovial inflammation, joint destruction, alveolar septal thickening, inflammatory cell infiltration, and collagen deposition. RT-qPCR demonstrated significant reductions in IL-6 and TNF-\u03b1 mRNA expression in joint and lung tissues, while Western blot analysis showed decreased pulmonary TGF-\u03b21 and \u03b1-SMA expression, indicating coordinated anti-inflammatory and anti-fibrotic effects. TWG also induced dose-dependent remodeling of the gut microbiota. High-dose TWG shifted the microbial community structure toward that of the NC group, increased the relative abundance of\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      and several butyrate-producing genera, and reduced\n                      <jats:italic>Desulfovibrio<\/jats:italic>\n                      ,\n                      <jats:italic>Bilophila<\/jats:italic>\n                      , and\n                      <jats:italic>Prevotella<\/jats:italic>\n                      . PICRUSt2 predicted enhanced metabolic potential for short-chain fatty acid-related pathways and reduced xenobiotic degradation in the TWG-H group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TWG, particularly in the high-dose group, exerted dual protective effects on joint and lung injury in CIA rats. These effects were associated with suppression of inflammatory cytokines and fibrosis-related proteins, with partial restoration of gut microbiota homeostasis. The findings support TWG as a potential anti-inflammatory and anti-fibrotic intervention for RA-ILD, although the microbiota-related effects remain associative and require further mechanistic validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1783503","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:35:51Z","timestamp":1776922551000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose-dependent protective effects of Tripterygium wilfordii glycosides on joint and lung injury and gut microbiota remodeling in collagen-induced arthritis rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Shangwen","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Henan University of Chinese Medicine","place":["Zhengzhou, Henan, China"]},{"name":"First Clinical Medical College, 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