title: Baicalin ameliorates experimental inflammatory bowel disease through polarization of macrophages to an M2 phenotype.
abstract: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract. Baicalin, originally isolated from the root of the Chinese herb Huangqin (Scutellaria baicalensis Georgi) and its main active ingredient, has a protective effect against inflammatory responses in several diseases. The present study investigated the effects of baicalin on macrophage polarization and its therapeutic role in IBD. Murine peritoneal macrophages and mice with colitis were treated with baicalin. Macrophage subset distribution, M1 and M2 macrophage-associated mRNA expression, and interferon regulatory factor 4 and 5 (IRF4 and IRF5) expression were analyzed. siRNA transfection into mouse peritoneal macrophages was utilized to suppress IRF4. Fluorescence-activated cell sorting, western blot, and real-time PCR analyses were performed. Baicalin (50μM) limited lipopolysaccharide (LPS)-induced M1 macrophage polarization; decreased LPS-induced tumor necrosis factor α, interleukin (IL)-23, and IRF5 expression; and increased IL-10, arginase-1 (Arg-1), and IRF4 expression. siRNA-mediated IRF4 silencing significantly impaired baicalin activity. Furthermore, pretreatment with baicalin (100mg/kg) in mice with dextran sodium sulfate (DSS)-induced colitis ameliorated the severity of colitis and significantly decreased the disease activity index (baicalin group, 3.33±0.52 vs. DSS group, 5.67±1.03). Baicalin (100mg/kg) also repressed IRF5 protein expression and promoted IRF4 protein expression in the lamina propria mononuclear cells, and induced macrophage polarization to the M2 phenotype. In summary, our results showed that baicalin upregulates IRF4 protein expression and reverses LPS-induced macrophage subset redistribution. Thus, baicalin alleviates DSS-induced colitis by modulating macrophage polarization to the M2 phenotype.
authors.affiliation: Department of Immunology, Mudanjiang Medical College, Mudanjiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Mudanjiang Medical College, Mudanjiang, China.
authors.forename: Zaishun
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Pathology, Mudanjiang Medical College, Mudanjiang, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Histoembryology, Mudanjiang Medical College, Mudanjiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Laboratory Animals, Mudanjiang Medical College, Mudanjiang, China.
authors.forename: Qingdong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Immunology, Mudanjiang Medical College, Mudanjiang, China.
authors.forename: Fujuan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Immunology, Mudanjiang Medical College, Mudanjiang, China.
authors.forename: Xuekui
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Immunology, Mudanjiang Medical College, Mudanjiang, China. Electronic address: xiaodongzhu@126.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Mudanjiang Medical College, Mudanjiang, China. Electronic address: xiaoli2595@126.com.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D031364:Scutellaria baicalensis / Q000276:immunology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D050835:Interferon Regulatory Factors; D034741:RNA, Small Interfering; D000099218:Interferon Regulatory Factor-4; C498178:Irf5 protein, mouse; C038044:baicalin
keywords: Baicalin; Colitis; IRF4; IRF5; M2 macrophage