{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T11:16:45Z","timestamp":1787915805730,"version":"build-2784847793"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"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 (RA) is a chronic autoimmune disease with limited therapeutic options, and current therapies are often associated with considerable adverse effects. Traditional Chinese medicinal plants such as\n                      <jats:italic>Cirsium japonicum<\/jats:italic>\n                      contain luteolin-7-O-rutinoside (lut-7-O-rutin), a flavonoid with reported anti-inflammatory activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim of the study<\/jats:title>\n                    <jats:p>\n                      Lut-7-O-rutin is a flavonoid compound found in various medicinal plants. This study aimed to investigate the therapeutic effects of lut-7-O-rutin on RA and elucidate the underlying mechanisms using both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      models, with a particular focus on the phosphatidylinositol 3-kinase\/protein kinase B\/nuclear factor-\u03baB (PI3K\/AKT\/NF-\u03baB) and cell cycle signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments, including ELISA, Western blotting, and immunofluorescence assays, were performed to evaluate the anti-inflammatory effects of lut-7-O-rutin on the IL-1\u03b2-induced inflammatory response in fibroblast-like synoviocytes (FLSs) derived from rat knee synovium. The effects of lut-7-O-rutin on the PI3K\/AKT\/NF-\u03baB and cell cycle signaling pathways were also examined.\n                      <jats:italic>In vivo<\/jats:italic>\n                      experiments were conducted to assess the therapeutic effects of lut-7-O-rutin administered by gastric gavage in collagen-induced arthritis (CIA) rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lut-7-O-rutin at 3.75\u00a0\u03bcg\/mL significantly reduced the levels of TNF-\u03b1, IL-6, and COX-2 in IL-1\u03b2-induced FLSs. It also decreased the phosphorylation levels of key components of the PI3K\/AKT\/NF-\u03baB signaling pathway, thereby attenuating inflammation. In addition, lut-7-O-rutin downregulated the expression of the cell cycle-associated proteins CDK4 and CCND and inhibited FLS proliferation.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , 21 days of lut-7-O-rutin administration by gastric gavage resulted in a significant reduction in arthritis scores, organ indices, and serum inflammatory mediator levels in CIA rats. Histopathological analysis showed that lut-7-O-rutin alleviated synovial inflammation, synovial hyperplasia, and bone erosion. Immunohistochemistry (IHC) analysis further showed that lut-7-O-rutin significantly inhibited the expression of key proteins in the PI3K\/AKT and cell cycle signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that lut-7-O-rutin alleviates joint inflammation and synovial hyperplasia in RA may be mediated through inhibiting the PI3K\/AKT\/NF-\u03baB signaling pathway and downregulating cell cycle-associated proteins, highlighting its potential as a therapeutic agent for RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1879862","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T10:28:02Z","timestamp":1787912882000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Luteolin-7-O-rutinoside alleviates rheumatoid arthritis through downregulation of the PI3K\/AKT\/NF-\u03baB and cell cycle signaling pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Weixi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering, College of Pharmaceutical Engineering and Life Science, Changzhou University","place":["Changzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The Affiliated Changzhou No.2 People\u2019s Hospital of Nanjing Medical University","place":["Changzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiding","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering, College of Pharmaceutical Engineering and Life Science, Changzhou University","place":["Changzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The Affiliated Changzhou No.2 People\u2019s Hospital of Nanjing Medical University","place":["Changzhou, China"]},{"name":"Changzhou Medical Center, Nanjing Medical University","place":["Changzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10753-017-0680-8","article-title":"The falconoid Luteolin mitigates the myocardial inflammatory response induced by high-Carbohydrate\/high-fat diet in wistar rats","volume":"41","author":"Abu-Elsaad","year":"2017","journal-title":"Inflammation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.pharep.2019.03.009","article-title":"Protection against nonalcoholic steatohepatitis through targeting IL-18 and IL-1alpha by luteolin","volume":"71","author":"Abu-Elsaad","year":"2019","journal-title":"Pharmacol. 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