title: Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice.
abstract: Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immune responses to microflora in genetically susceptible hosts. A major challenge for IBD research is to develop new strategies for treating this disease. Berberine, an alkaloid derived from plants, is an alternative medicine for treating bacterial diarrhea and intestinal parasite infections. Recent studies suggest that berberine exerts several other beneficial effects, including inducing anti-inflammatory responses. This study determined the effect of berberine on treating dextran sulfate sodium (DSS)-induced intestinal injury and colitis in mice. Berberine was administered through gavage to mice with established DSS-induced intestinal injury and colitis. Clinical parameters, intestinal integrity, proinflammatory cytokine production, and signaling pathways in colonic macrophages and epithelial cells were determined. Berberine ameliorated DSS-induced body weight loss, myeloperoxidase activity, shortening of the colon, injury, and inflammation scores. DSS-upregulated proinflammatory cytokine levels in the colon, including TNF, IFN-γ, KC, and IL-17 were reduced by berberine. Berberine decreased DSS-induced disruption of barrier function and apoptosis in the colon epithelium. Furthermore, berberine inhibited proinflammatory cytokine production in colonic macrophages and epithelial cells in DSS-treated mice and promoted apoptosis of colonic macrophages. Activation of signaling pathways involved in stimulation of proinflammatory cytokine production, including MAPK and NF-κB, in colonic macrophages and epithelial cells from DSS-treated mice was decreased by berberine. In summary, berberine promotes recovery of DSS-induced colitis and exerts inhibitory effects on proinflammatory responses in colonic macrophages and epithelial cells. Thus berberine may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA. fang.yan@vanderbilt.edu
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.forename: Lihong
authors.initials: L
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Hanwei
authors.initials: H
authors.lastname: Cao
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Rupesh
authors.initials: R
authors.lastname: Chaturvedi
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Israel
authors.forename: Hailong
authors.initials: H
authors.lastname: Cao
authors.forename: Bangmao
authors.initials: B
authors.lastname: Wang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
authors.forename: D Brent
authors.initials: DB
authors.lastname: Polk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000166:cytology / Q000503:physiopathology; D016207:Cytokines / Q000187:drug effects; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D016264:Dextran Sulfate