{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T06:23:57Z","timestamp":1787207037016,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Rheumatoid arthritis (RA) is a chronic inflammatory joint disease and the leading cause of joint-related limb disability. Traditional Chinese Medicine (TCM) offers certain advantages in RA treatment, and Tripterygium preparations are widely used due to their significant clinical efficacy. This study aimed to investigate the mechanism of action of Tripterygium Glycosides Tablets (TG) in the treatment of RA through\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      experiments, providing a theoretical basis for clinical application.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A collagen-induced arthritis (CIA) rat model was established, and the rats received oral administration of the corresponding drugs or distilled water for 4 weeks. The therapeutic effect and mechanism of TG on CIA rats were evaluated by comparing joint swelling severity, radiographic changes in the synovium, and alterations in the JAK\/STAT signaling pathway and related inflammatory factors. Further\n                      <jats:italic>ex vivo<\/jats:italic>\n                      experiments were performed using fibroblast-like synoviocytes (FLS) as the research subject. Lentiviral infection technology was used to overexpress IGF1 or interfere with the expression of Lnc-ENST00000602558. Drug-containing serum was used for intervention. The mechanism of TG in treating RA was further elucidated by detecting changes in cell migration ability, the expression of IGF1 and Lnc-ENST00000602558, JAK\/STAT pathway-related targets, and inflammatory factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TG significantly improved joint swelling, bone and cartilage destruction in CIA rats, reduced synovial tissue hyperplasia, inhibited the JAK\/STAT pathway and IGF1 in the rat joint synovium, lowered serum levels of the inflammatory factors TNF-\u03b1 and IL-1\u03b2, alleviated joint damage, and delayed disease progression.\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      experiments showed that the Lnc-ENST00000602558\/IGF1 axis could activate the JAK\/STAT pathway in FLS. When Lnc-ENST00000602558 was expressed at low levels, the regulatory capacity of TG on the Lnc-ENST00000602558\/IGF1 axis and the JAK\/STAT pathway was diminished.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TG may regulate the JAK\/STAT pathway via the Lnc-ENST00000602558\/IGF1 axis, thereby inhibiting the inflammatory response, mitigating bone and cartilage destruction, and delaying disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1864355","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:28:49Z","timestamp":1787203729000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the mechanism of action of tripterygium glycosides tablets in the treatment of rheumatoid arthritis based on the Lnc-ENST00000602558\/IGF1 signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Jin-ying","family":"Fang","sequence":"first","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-nan","family":"Yang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cun-xiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-hua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Hu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Lv","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-hong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-long","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1158\/1535-7163.mct-22-0323","article-title":"JAK: not just another kinase","volume":"21","author":"Agashe","year":"2022","journal-title":"Mol. Cancer Therapeut."},{"key":"B2","doi-asserted-by":"publisher","first-page":"415","DOI":"10.3390\/ijms22010415","article-title":"GH\/IGF-1 abnormalities and muscle impairment: from basic research to clinical practice","volume":"22","author":"Biagetti","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"114147","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/j.autrev.2019.05.007","article-title":"Challenges in the treatment of rheumatoid arthritis","volume":"18","author":"Conigliaro","year":"2019","journal-title":"Autoimmun. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"111052","DOI":"10.1016\/j.mce.2020.111052","article-title":"Effects of GH\/IGF axis on bone and cartilage","volume":"519","author":"Dixit","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1080\/08923973.2022.2092748","article-title":"Tetrandrine-induced downregulation of lncRNA NEAT1 inhibits rheumatoid arthritis progression through the STAT3\/miR-17-5p pathway","volume":"44","author":"Duan","year":"2022","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"8172","DOI":"10.1038\/s41467-023-44053-w","article-title":"The long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis","volume":"14","author":"Elhai","year":"2023","journal-title":"Nat. Commun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1111\/jcmm.17228","article-title":"JAK-STAT core cancer pathway: an integrative cancer interactome analysis","volume":"26","author":"Erdogan","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1002\/art.10705","article-title":"Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years","volume":"48","author":"Gabriel","year":"2003","journal-title":"Arthritis Rheumatism"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e1098","DOI":"10.1002\/iid3.1098","article-title":"The Lnc-ENST00000602558\/IGF1 axis as a predictor of response to treatment with tripterygium glycosides in rheumatoid arthritis patients","volume":"12","author":"Gao","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.phymed.2018.12.030","article-title":"Comparison of combination therapy with methotrexate and sinomenine or leflunomide for active rheumatoid arthritis: a randomized controlled clinical trial","volume":"57","author":"Huang","year":"2019","journal-title":"Phytomed. Int. J.Phytother. Phytopharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"103725","DOI":"10.1016\/j.tice.2026.103725","article-title":"Cordia myxa abrogates rheumatoid synoviocytes through inhibiting inflammatory responses and expression profiles of the TNF-\u03b1 and COX-2 signaling pathway in a rodent model","volume":"103","author":"Jad","year":"2026","journal-title":"Tissue Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1087925","DOI":"10.3389\/fimmu.2023.1087925","article-title":"Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis","volume":"14","author":"Jiang","year":"2023","journal-title":"Front. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"150211","DOI":"10.1016\/j.gene.2026.150211","article-title":"Differential expression patterns of circulating NEAT1, HOTAIR, and miR-23b in rheumatoid arthritis","volume":"1003","author":"Jumaa","year":"2026","journal-title":"Implic. Mol. Diagnos."},{"key":"B15","doi-asserted-by":"publisher","first-page":"560","DOI":"10.3390\/ijms26020560","article-title":"The role of long non-coding RNA in rheumatoid arthritis","volume":"26","author":"Kie\u0142bowski","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"7736","DOI":"10.3390\/ijms24097736","article-title":"Viral vector-based gene therapy","volume":"24","author":"Li","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"608703","DOI":"10.3389\/fphar.2020.608703","article-title":"Clinical practice guideline for tripterygium glycosides\/tripterygium wilfordii tablets in the treatment of rheumatoid arthritis","volume":"11","author":"Lin","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2228","DOI":"10.3389\/fimmu.2018.02228","article-title":"Sinomenine inhibits the progression of rheumatoid arthritis by regulating the secretion of inflammatory cytokines and monocyte\/macrophage subsets","volume":"9","author":"Liu","year":"2018","journal-title":"Front. Immunology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4939-8802-0_1","article-title":"Collagen-induced arthritis models","volume":"2766","author":"Miyoshi","year":"2024","journal-title":"Method. Mol. Biol. Clift. N.J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1093\/intimm\/dxr077","article-title":"IL-1\u03b2 and TNF\u03b1-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis","volume":"23","author":"Mori","year":"2011","journal-title":"Int. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"572858","DOI":"10.3389\/fimmu.2020.572858","article-title":"Th17\/Treg-related transcriptional factor expression and cytokine profile in patients with rheumatoid arthritis","volume":"11","author":"Paradowska-Gorycka","year":"2020","journal-title":"Front. Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e70736","DOI":"10.1111\/1756-185x.70736","article-title":"Garcinia cowa bark extract attenuates collagen-induced arthritis via inhibition of oxidative stress in rats","volume":"29","author":"Pradhan","year":"2026","journal-title":"Int. J. Rheum. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.2174\/1381612828666220324124720","article-title":"Circumstantial insights into the potential of traditional Chinese medicinal plants as a therapeutic approach in rheumatoid arthritis","volume":"28","author":"Sharma","year":"2022","journal-title":"Curr. Pharmaceut. Design"},{"key":"B24","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.lfs.2017.08.036","article-title":"SOCS2 exacerbates myocardial injury induced by ischemia\/reperfusion in diabetic mice and H9c2 cells through inhibiting the JAK-STAT-IGF-1 pathway","volume":"188","author":"Sheng","year":"2017","journal-title":"Life Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"112148","DOI":"10.1016\/j.ejmech.2020.112148","article-title":"Design, synthesis, and pharmacological evaluation of 4- or 6-phenyl-pyrimidine derivatives as novel and selective Janus kinase 3 inhibitors","volume":"191","author":"Shu","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet (London, Engl.)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"Itc1","DOI":"10.7326\/aitc201901010","article-title":"Rheumatoid Arthritis","volume":"170","author":"Sparks","year":"2019","journal-title":"Ann. Int. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s10735-026-10875-3","article-title":"Wenyang Yishen Tongluo prescription synergizes with bone marrow mesenchymal stem cells to alleviate rheumatoid arthritis via inhibiting IL-6","volume":"57","author":"Su","year":"2026","journal-title":"J. Mol. Histol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"114368","DOI":"10.1016\/j.jep.2021.114368","article-title":"Traditional herbal medicine: therapeutic potential in rheumatoid arthritis","volume":"279","author":"Wang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"792884","DOI":"10.3389\/fimmu.2021.792884","article-title":"LncRNA expression profiles in systemic lupus erythematosus and rheumatoid arthritis: emerging biomarkers and therapeutic targets","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"106210","DOI":"10.1016\/j.intimp.2020.106210","article-title":"The role of JAK\/STAT signaling pathway and its inhibitors in diseases","volume":"80","author":"Xin","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/s41392-023-01468-7","article-title":"Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer","volume":"8","author":"Xue","year":"2023","journal-title":"Signal Transduct. Targeted Ther."},{"key":"B33","doi-asserted-by":"publisher","first-page":"106549","DOI":"10.1016\/j.phrs.2022.106549","article-title":"The role of non-coding RNAs (miRNA and lncRNA) in the clinical management of rheumatoid arthritis","volume":"186","author":"Yang","year":"2022","journal-title":"Pharmacol. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"103148","DOI":"10.1016\/j.jaut.2023.103148","article-title":"International consensus guidance for the use of Tripterygium Wilfordii Hook F in the treatment of active rheumatoid arthritis","volume":"142","author":"Zhang","year":"2023","journal-title":"J. Autoimmun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s13075-018-1563-6","article-title":"Comparison of the impact of Tripterygium wilfordii Hook F and methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study","volume":"20","author":"Zhou","year":"2018","journal-title":"Arthritis Res. Ther."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1864355\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:28:51Z","timestamp":1787203731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1864355\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":35,"alternative-id":["10.3389\/fphar.2026.1864355"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1864355","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]},"article-number":"1864355"}}