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Paeoniflorin\u20106\u2032\u2010<jats:italic>O<\/jats:italic>\u2010benzene sulfonate (CP\u201025) has been shown to exert anti\u2010inflammatory immune regulatory effects in animal models of inflammatory autoimmune disease. This study aimed to investigate the of GRK2 in the pathogenesis of ulcerative colitis (UC) and its effects on macrophage polarization, macrophage subtype regulation of intestinal barrier function, and therapeutic effects of CP\u201025 in mice with DSS\u2010induced colitis. We found imbalanced macrophage polarization, intestinal barrier dysfunction, and abnormal activation of GRK2 and TLR4\u2010NF\u2010\u03baB\u2010NLRP3 inflammasome signaling pathway in the colonic mucosa of patients with UC. CP\u201025, restored the damaged intestinal barrier function by inhibiting the transmembrane region of GRK2 in macrophages stimulated by lipopolysaccharides. CP\u201025 exerted therapeutic effects by ameliorating clinical manifestation, regulating macrophage polarization, and restoring abnormally activated TLR4\u2010NF\u2010\u03baB\u2010NLRP3 inflammasome signaling pathway by inhibiting GRK2. These data suggest the pathogenesis of UC may be related to the imbalance of macrophage polarization, which leads to abnormal activation of TLR4\u2010NF\u2010\u03baB\u2010NLRP3 inflammasome signaling pathway mediated by GRK2 and destruction of the intestinal mucosal barrier. CP\u201025 confers therapeutic effects on colitis by inhibiting GRK2 translocation to induce the downregulation of TLR4\u2010NF\u2010\u03baB\u2010NLRP3 inflammasome signaling in macrophages.<\/jats:p>","DOI":"10.1002\/iub.2564","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T07:59:28Z","timestamp":1632988768000},"page":"1406-1422","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp>CP<\/scp>\u201025 exerts therapeutic effects in mice with dextran sodium sulfate\u2010induced colitis by inhibiting <scp>GRK2<\/scp> translocation to downregulate the <scp>TLR4\u2010NF\u2010\u03baB\u2010NLRP3<\/scp> inflammasome signaling pathway in macrophages"],"prefix":"10.1002","volume":"73","author":[{"given":"Ying","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti\u2010inflammatory and Immune 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