{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:56:48Z","timestamp":1793044608767,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"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><jats:title>Purpose<\/jats:title><jats:p>Wuwei Kushen Changrong capsule (Composite <jats:italic>Sophora<\/jats:italic> Colon-soluble Capsule, CSCC) is a Chinese patent medicine developed to treat ulcerative colitis. Studies highlight CSCC potential efficacy for ulcerative colitis (UC) but unclear mechanism limits its widely treatment for patients. We aimed to investigate the anti-colitis efficacy of CSCC and explore the mechanism by which GPR43 inhibits the NLRP3\/STAT3 signaling pathway, thereby mediating the protective effects of CSCC on the intestinal barrier.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The protective effects of CSCC were evaluated in a murine ulcerative colitis model induced by 3% DSS. Assessments included body weight, Disease Activity Index (DAI) score, colon length, and histopathological score. Colon tissue, cell function, and immune-inflammatory status were evaluated using immunohistochemistry, immunofluorescence, ELISA, and real-time fluorescence quantitative PCR (RT-PCR). Protein expression levels of relevant pathways and receptors were measured using Western blot. All experiments were repeated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CSCC protected mice from DSS-induced colitis by upregulating Gpr43, promoting the expression of ZO-1 and Occludin tight junction proteins. Mechanistically, CSCC inhibits the MEK4\/JNK1\/STAT3 activation pathway, consequently suppressing the STAT3\/NLRP3\/IL-1\u03b2 pathway and inhibiting the production of inflammatory factors such as IL-17A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The mechanisms through which CSCC protects against DSS-induced colitis may include upregulating Gpr43, inhibiting the STAT3\/NLRP3 pathway, and suppressing inflammation factors like IL-17A. These findings highlight the mechanisms underlying CSCC\u2019s anti-colitis effects and suggest its potential as a therapeutic candidate for managing the progression of UC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1423012","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T12:21:57Z","timestamp":1730722917000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Wuwei Kushen Changrong capsule alleviates DSS-induced colitis in mice via inhibition of NLRP3 inflammasome and STAT3 pathway"],"prefix":"10.3389","volume":"15","author":[{"given":"Mingjun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengheng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxiong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhanQi","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.clnu.2019.11.002","article-title":"ESPEN practical guideline: clinical Nutrition in inflammatory bowel disease","volume":"39","author":"Bischoff","year":"2020","journal-title":"Clin. Nutr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"603476","DOI":"10.3389\/fphar.2020.603476","article-title":"Efficacy and safety of Sophora flavescens (kushen) based traditional Chinese medicine in the treatment of ulcerative colitis: clinical evidence and potential mechanisms","volume":"11","author":"Chen","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1007\/s11655-022-3317-1","article-title":"Composite Sophora colon-soluble capsule ameliorates DSS-induced ulcerative colitis in mice via gut microbiota-derived butyric acid and NCR(+) ILC3","volume":"29","author":"Chen","year":"","journal-title":"Chin. J. Integr. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1093\/ibd\/izad099","article-title":"SIRT3 activator honokiol inhibits Th17 cell differentiation and alleviates colitis","volume":"29","author":"Chen","year":"","journal-title":"Inflamm. Bowel Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1069694","DOI":"10.3389\/fmicb.2022.1069694","article-title":"Pectin supplement alleviates gut injury potentially through improving gut microbiota community in piglets","volume":"13","author":"Dang","year":"2022","journal-title":"Front. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"9318721","DOI":"10.1155\/2022\/9318721","article-title":"The attenuation of chronic ulcerative colitis by (R)-salbutamol in repeated DSS-induced mice","volume":"2022","author":"Deng","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"9521073","DOI":"10.1155\/2020\/9521073","article-title":"Integrating pharmacology and microbial network analysis with experimental validation to reveal the mechanism of composite Sophora colon-soluble capsule against ulcerative colitis","volume":"2020","author":"Ding","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.gtc.2020.07.005","article-title":"Epidemiology and pathogenesis of ulcerative colitis","volume":"49","author":"Du","year":"2020","journal-title":"Gastroenterol. Clin. North Am."},{"key":"B9","doi-asserted-by":"publisher","first-page":"105125","DOI":"10.1016\/j.micinf.2023.105125","article-title":"Microbiota-gut-adipose axis: butyrate-mediated the improvement effect on inflammatory response and fatty acid oxidation dysregulation attenuates obesity in sleep-restricted mice","volume":"25","author":"Gao","year":"2023","journal-title":"Microbes Infect."},{"key":"B10","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.jep.2011.08.057","article-title":"Efficacy and safety of Fufangkushen colon-coated capsule in the treatment of ulcerative colitis compared with mesalazine: a double-blinded and randomized study","volume":"141","author":"Gong","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1093\/ecco-jcc\/jjw186","article-title":"Long-term inflammation transforms intestinal epithelial cells of colonic organoids","volume":"11","author":"Hibiya","year":"2017","journal-title":"J. Crohns Colitis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1093\/ecco-jcc\/jjac020","article-title":"Role of nutrient-sensing receptor GPRC6A in regulating colonic group 3 innate lymphoid cells and inflamed mucosal healing","volume":"16","author":"Hou","year":"2022","journal-title":"J. Crohns Colitis"},{"key":"B13","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3760\/cma.j.cn311367-20240125-00036","article-title":"Chinese clinical practice guideline on the management of ulcerative colitis (2023, Xi\u2032an)","volume":"8","author":"Kaichun","year":"2024","journal-title":"Chin. J. Inflamm. Bowel Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"695576","DOI":"10.3389\/fimmu.2022.695576","article-title":"PI3K signaling in dendritic cells aggravates DSS-induced colitis","volume":"13","author":"Kuttke","year":"2022","journal-title":"Front. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1093\/ecco-jcc\/jju007","article-title":"Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases","volume":"9","author":"Langhorst","year":"2015","journal-title":"J. Crohns Colitis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1080\/15548627.2019.1635384","article-title":"New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD","volume":"16","author":"Larabi","year":"2020","journal-title":"Autophagy"},{"key":"B17","doi-asserted-by":"publisher","first-page":"153814","DOI":"10.1016\/j.phymed.2021.153814","article-title":"Bryodulcosigenin a natural cucurbitane-type triterpenoid attenuates dextran sulfate sodium (DSS)-induced colitis in mice","volume":"94","author":"Li","year":"2022","journal-title":"Phytomedicine"},{"key":"B18","doi-asserted-by":"publisher","first-page":"116215","DOI":"10.1016\/j.jep.2023.116215","article-title":"Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis","volume":"308","author":"Li","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"123331","DOI":"10.1016\/j.envpol.2024.123331","article-title":"Oil mistparticulate matter exposure induces hyperlipidemia-related inflammation via microbiota\/SCFAs\/GPR43 axis inhibition and TLR4\/NF-\u03baB activation","volume":"344","author":"Liu","year":"2024","journal-title":"Environ. Pollut."},{"key":"B20","doi-asserted-by":"publisher","first-page":"114586","DOI":"10.1016\/j.biopha.2023.114586","article-title":"Microbiota-derived short-chain fatty acids and modulation of host-derived peptides formation: focused on host defense peptides","volume":"162","author":"Liu","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B21","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.ebiom.2019.02.050","article-title":"NCR(-) group 3 innate lymphoid cells orchestrate IL-23\/IL-17 axis to promote hepatocellular carcinoma development","volume":"41","author":"Liu","year":"2019","journal-title":"EBioMedicine"},{"key":"B22","doi-asserted-by":"publisher","first-page":"117262","DOI":"10.1016\/j.jep.2023.117262","article-title":"Fuling-Zexie formula attenuates hyperuricemia-induced nephropathy and inhibits JAK2\/STAT3 signaling and NLRP3 inflammasome activation in mice","volume":"319","author":"Lu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"154660","DOI":"10.1016\/j.phymed.2023.154660","article-title":"Modified Gegen Qinlian decoction ameliorates DSS-induced chronic colitis in mice by restoring the intestinal mucus barrier and inhibiting the activation of \u03b3\u03b4T17 cells","volume":"111","author":"Ma","year":"2023","journal-title":"Phytomedicine"},{"key":"B24","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1007\/s10495-019-01542-y","article-title":"17-Aminogeldanamycin selectively diminishes IRE1\u03b1-XBP1s pathway activity and cooperatively induces apoptosis with MEK1\/2 and BRAFV600E inhibitors in melanoma cells of different genetic subtypes","volume":"24","author":"Mielczarek-Lewandowska","year":"2019","journal-title":"Apoptosis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41586-019-1844-5","article-title":"Somatic inflammatory gene mutations in human ulcerative colitis epithelium","volume":"577","author":"Nanki","year":"2020","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2147\/DDDT.S446949","article-title":"Plants with anti-ulcer activity and mechanism: a review of preclinical and clinical studies","volume":"18","author":"Prayoga","year":"2024","journal-title":"Drug Des. Devel Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"116396","DOI":"10.1016\/j.jep.2023.116396","article-title":"The potential mechanism of qinghua quyu jianpi decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation","volume":"310","author":"Qu","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/cmi.2016.35","article-title":"The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18\/IL-22\/STAT3 pathway","volume":"14","author":"Ratsimandresy","year":"2017","journal-title":"Cell Mol. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"384","DOI":"10.14309\/ajg.0000000000000152","article-title":"ACG clinical guideline: ulcerative colitis in adults","volume":"114","author":"Rubin","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1056\/NEJMoa2033617","article-title":"Ozanimod as induction and maintenance therapy for ulcerative colitis","volume":"385","author":"Sandborn","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e1539","DOI":"10.1002\/ctm2.1539","article-title":"ARID5B-mediated LINC01128 epigenetically activated pyroptosis and apoptosis by promoting the formation of the BTF3\/STAT3 complex in \u03b22GPI\/anti-\u03b22GPI-treated monocytes","volume":"14","author":"Tan","year":"2024","journal-title":"Clin. Transl. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1007\/s11655-010-0562-5","article-title":"A multi-center, randomized, single-blind, controlled clinical study on the efficacy of composite sophora colon-soluble capsules in treating ulcerative colitis","volume":"16","author":"Tong","year":"2010","journal-title":"Chin. J. Integr. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jtos.2024.01.005","article-title":"Short chain fatty acids inhibit corneal inflammatory responses to TLR ligands via the ocular G-protein coupled receptor 43","volume":"32","author":"Wu","year":"2024","journal-title":"Ocul. Surf."},{"key":"B34","doi-asserted-by":"publisher","first-page":"4475","DOI":"10.3390\/nu14214475","article-title":"Co-cultures of Lactobacillus acidophilus and Bacillus subtilis enhance mucosal barrier by modulating gut microbiota-derived short-chain fatty acids","volume":"14","author":"Xie","year":"2022","journal-title":"Nutrients"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2782112","DOI":"10.1155\/2022\/2782112","article-title":"Kui jie Tong ameliorates ulcerative colitis by regulating gut microbiota and NLRP3\/caspase-1 classical pyroptosis signaling pathway","volume":"2022","author":"Xue","year":"2022","journal-title":"Dis. Markers"},{"key":"B36","doi-asserted-by":"publisher","first-page":"154455","DOI":"10.1016\/j.phymed.2022.154455","article-title":"Tongxie-Yaofang formula regulated macrophage polarization to ameliorate DSS-induced colitis via NF-\u03baB\/NLRP3 signaling pathway","volume":"107","author":"Zhang","year":"2022","journal-title":"Phytomedicine"},{"key":"B37","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13046-021-01844-7","article-title":"LncRNA CBR3-AS1 regulates of breast cancer drug sensitivity as a competing endogenous RNA through the JNK1\/MEK4-mediated MAPK signal pathway","volume":"40","author":"Zhang","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1002\/ptr.8087","article-title":"International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by board of specialty committee of digestive system disease of world federation of Chinese medicine societies (2023)","volume":"38","author":"Zhang","year":"2024","journal-title":"Phytother. Res."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1423012\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T12:22:00Z","timestamp":1730722920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1423012\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,12]]},"references-count":38,"alternative-id":["10.3389\/fphar.2024.1423012"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1423012","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,12]]},"article-number":"1423012"}}