{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:05:10Z","timestamp":1790057110071,"version":"4.0.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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>Introduction<\/jats:title>\n                    <jats:p>Inflammatory bowel disease (IBD) has an intricate pathophysiology that greatly impacts patients\u2019 quality of life. Wumei Wan, a traditional Chinese medicinal formulation, exhibits specific therapeutic effects on IBD. Kaempferol (KF), an active ingredient in Wumei Wan, may significantly contribute to IBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 2% DSS-induced chronic colitis mouse model was established, randomly divided into six groups and treated with KF. Relevant indicators of chronic colitis were measured, including body weight, Disease Activity Index (DAI), colon length, histological alterations, as well as indicators of inflammatory factors, fibrosis, intestinal barrier function, hepatic and renal function, and oxidative stress. TNF-\u03b1 was employed to stimulate colonic epithelial cells in cell studies. After KF intervention, cytotoxicity, transforming growth factor-\u03b21 (TGF-\u03b21), and cell survival were observed to investigate its impact on IBD. The HT29\/CCD-18Co medium with TNF-\u03b1\/TNF-\u03b1+KF was co-cultured with CCD-18Co\/HT29 cells, and a cell line with heme oxygenase 1 (HMOX1) silencing\/overexpression was generated to explore the impact of KF on intestinal epithelial cell-fibroblast crosstalk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      , KF therapy increased body weight, reduced DAI, and improved colon length as well as histopathology. Furthermore, KF reversed the elevated levels of inflammatory cytokines, intestinal barrier function, and oxidative stress markers observed in the model group.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , KF reversed TNF-\u03b1-induced decrease of intestinal epithelial cells, TGF-\u03b21 downregulation, regulated cell function, and reduced inflammation. KF may suppress TNF-\u03b1-induced fibroblast activation, and HMOX1 was crucial for regulating cell crosstalk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, KF mitigates IBD by modulating intestinal epithelial-fibroblast interaction, suppressing inflammatory responses, reducing intestinal fibrosis, and increasing intestinal mucosal barrier function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1799034","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:38:55Z","timestamp":1790055535000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Kaempferol in inflammatory bowel disease: regulating intestinal epithelial-fibroblast crosstalk"],"prefix":"10.3389","volume":"17","author":[{"given":"Haixin","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Anorectal Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou City, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, the Third Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou City, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Anorectal Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou City, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou City, Zhejiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"857015","DOI":"10.3389\/fphar.2022.857015","article-title":"Kaempferol from Penthorum chinense pursh attenuates hepatic ischemia\/reperfusion injury by suppressing oxidative stress and inflammation through activation of the Nrf2\/HO-1 signaling pathway","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.3390\/antiox12081642","article-title":"A critical review of kaempferol in intestinal health and diseases","volume":"12","author":"Chen","year":"2023","journal-title":"Antioxidants"},{"key":"B3","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.jare.2024.11.016","article-title":"Kaempferol regulating macrophage foaming and atherosclerosis through Piezo1-mediated MAPK\/NF-\u03baB and Nrf2\/HO-1 signaling pathway","volume":"75","author":"Chu","year":"2024","journal-title":"J. Adv. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6416","DOI":"10.3390\/ijms25126416","article-title":"Inflammatory bowel disease: immune function, tissue fibrosis and current therapies","volume":"25","author":"Cos\u00edn-Roger","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B35","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26115151","article-title":"Quercetin, kaempferol and capsaicin counteract the TGF-\u03b21-induced upregulation of \u03b1SMA and Collagen in Myoblasts","volume":"26","author":"Cuijpers","year":"2025","journal-title":"Int J Mol Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.crohns.2012.04.008","article-title":"Proinflammatory cytokines induce crosstalk between colonic epithelial cells and subepithelial myofibroblasts: implication in intestinal fibrosis","volume":"7","author":"Drygiannakis","year":"2013","journal-title":"J. Crohn's Colitis"},{"key":"B34","first-page":"Cd008414","article-title":"Oral 5-aminosalicylic acid for maintenance of surgically-induced remission in Crohn\u2019s disease","author":"Gordon","year":"2011","journal-title":"Cochrane Database Syst Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"106610","DOI":"10.1016\/j.intimp.2020.106610","article-title":"PIK3R3 regulates ZO-1 expression through the NF-kB pathway in inflammatory bowel disease","volume":"85","author":"Ibrahim","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1186\/s12967-024-05058-1","article-title":"Predictive biomarkers for anti-TNF alpha therapy in IBD patients","volume":"22","author":"Kumar","year":"2024","journal-title":"J. Transl. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1053\/j.gastro.2021.08.047","article-title":"The tight junction protein ZO-1 is dispensable for barrier function but critical for effective mucosal repair","volume":"161","author":"Kuo","year":"2021","journal-title":"Gastroenterology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"331","DOI":"10.3892\/ijmm.2012.1204","article-title":"Kaempferol suppresses lipid accumulation in macrophages through the downregulation of cluster of differentiation 36 and the upregulation of scavenger receptor class B type I and ATP-binding cassette transporters A1 and G1","volume":"31","author":"Li","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1186\/s13046-022-02536-6","article-title":"Crenigacestat blocking notch pathway reduces liver fibrosis in the surrounding ecosystem of intrahepatic CCA viaTGF-\u03b2 inhibition","volume":"41","author":"Mancarella","year":"2022","journal-title":"J. Exp. and Clin. Cancer Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"G936","DOI":"10.1152\/ajpgi.00053.2021","article-title":"Colon epithelial cell TGF\u03b2 signaling modulates the expression of tight junction proteins and barrier function in mice","volume":"320","author":"Marincola Smith","year":"2021","journal-title":"Am. J. Physiol Gastrointest Liver Physiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"15054","DOI":"10.3390\/ijms232315054","article-title":"Kaempferol: antimicrobial properties, sources, clinical, and traditional applications","volume":"23","author":"Periferakis","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"679897","DOI":"10.3389\/fimmu.2021.679897","article-title":"Kaempferol alleviates murine experimental colitis by restoring gut microbiota and inhibiting the LPS-TLR4-NF-\u03baB axis","volume":"12","author":"Qu","year":"2021","journal-title":"Front. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1136\/gutjnl-2023-329963","article-title":"Fibrosis in IBD: from pathogenesis to therapeutic targets","volume":"73","author":"Rieder","year":"2024","journal-title":"Gut"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.3390\/nu15071771","article-title":"Pomegranate extract affects gut biofilm forming bacteria and promotes intestinal mucosal healing regulating the crosstalk between epithelial cells and intestinal fibroblasts","volume":"15","author":"Rizzo","year":"2023","journal-title":"Nutrients"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.3389\/fimmu.2018.01956","article-title":"Heme Oxygenase-1 as a modulator of intestinal inflammation development and progression","volume":"9","author":"Sebasti\u00e1n","year":"2018","journal-title":"Front. Immunol."},{"key":"B32","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1093\/ecco-jcc\/jjy004","article-title":"Primary non-response to tumor necrosis factor antagonists is associated with inferior response to second-line biologics in patients with inflammatory bowel diseases: a systematic review and meta-analysis","volume":"12","author":"Singh","year":"2018","journal-title":"J. Crohns Colitis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1002\/ueg2.12319","article-title":"Environmental risk factors for inflammatory bowel disease","volume":"10","author":"Singh","year":"2022","journal-title":"United Eur. Gastroenterology J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.3748\/wjg.v29.i18.2733","article-title":"Study of tumor necrosis factor receptor in the inflammatory bowel disease","volume":"29","author":"Souza","year":"2023","journal-title":"World J. Gastroenterology"},{"key":"B38","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/2211068214561025","article-title":"TEER measurement techniques for in vitro barrier model systems","volume":"20","author":"Srinivasan","year":"2015","journal-title":"J. Lab. Autom."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8847","DOI":"10.3390\/ijms22168847","article-title":"Kaempferol and kaempferide attenuate oleic acid-induced lipid accumulation and oxidative stress in HepG2 cells","volume":"22","author":"Tie","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.3390\/ijms22041790","article-title":"HGF and TSG-6 released by mesenchymal stem cells attenuate Colon radiation-induced fibrosis","volume":"22","author":"Usunier","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"542","DOI":"10.3390\/cancers16030542","article-title":"Pancreatic tumor organoid-derived factors from cachectic patients disrupt contractile smooth muscle cells","volume":"16","author":"Vaes","year":"2024","journal-title":"Cancers"},{"key":"B22","doi-asserted-by":"publisher","first-page":"34607","DOI":"10.1039\/c9ra06222j","article-title":"Impact of deoxynivalenol and kaempferol on expression of tight junction proteins at different stages of Caco-2 cell proliferation and differentiation","volume":"9","author":"Wang","year":"2019","journal-title":"RSC Adv."},{"key":"B23","doi-asserted-by":"publisher","first-page":"670159","DOI":"10.3389\/fimmu.2021.670159","article-title":"Therapeutic targeting of Nrf2 signaling by maggot extracts ameliorates inflammation-associated intestinal fibrosis in chronic DSS-induced colitis","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"887497","DOI":"10.3389\/fphar.2022.887497","article-title":"Metformin ameliorates chronic colitis-related intestinal fibrosis via inhibiting TGF-\u03b21\/Smad3 signaling","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1089809","DOI":"10.3389\/fimmu.2023.1089809","article-title":"Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2\/HO-1 signaling pathway","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s12951-024-02439-y","article-title":"The mitochondria-targeted kaempferol nanoparticle ameliorates severe acute pancreatitis","volume":"22","author":"Wen","year":"2024","journal-title":"J. Nanobiotechnology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"112580","DOI":"10.1016\/j.jep.2020.112580","article-title":"Wu-Mei-Wan ameliorates chronic colitis-associated intestinal fibrosis through inhibiting fibroblast activation","volume":"252","author":"Wu","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.3892\/mmr.2026.13805","article-title":"Naringin ameliorates intestinal injury in ulcerative colitis model mice by modulating the JAK2\/STAT3 signaling pathway","volume":"33","author":"Wu","year":"2026","journal-title":"Molecular medicine reports"},{"key":"B29","doi-asserted-by":"publisher","first-page":"690736","DOI":"10.3389\/fphar.2021.690736","article-title":"Kaempferol alleviates steatosis and inflammation during early non-alcoholic steatohepatitis associated with liver X receptor \u03b1-Lysophosphatidylcholine acyltransferase 3 signaling pathway","volume":"12","author":"Xiang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.3389\/fphar.2020.01118","article-title":"Kaempferol protects blood vessels from damage induced by oxidative stress and inflammation in association with the Nrf2\/HO-1 signaling pathway","volume":"11","author":"Yao","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s10020-018-0053-2","article-title":"Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-\u03baB\/HIF-1\u03b1 pathway by binding to HMOX1 in rats with sepsis","volume":"24","author":"Zhan","year":"2018","journal-title":"Mol. Med."},{"key":"B33","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/apt.16723","article-title":"Trends in the use of biologicals and their treatment outcomes among patients with inflammatory bowel diseases - a Danish nationwide cohort study","volume":"55","author":"Zhao","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B36","doi-asserted-by":"crossref","first-page":"783254","DOI":"10.3389\/fimmu.2022.783254","article-title":"BAFF Blockade Attenuates DSS-Induced Chronic Colitis via Inhibiting NLRP3 Inflammasome and NF-\u03baB Activation","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Immunol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1799034\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:38:56Z","timestamp":1790055536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1799034\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":37,"alternative-id":["10.3389\/fphar.2026.1799034"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1799034","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1799034"}}