title: Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-κB signaling and T-helper cell homeostasis.
abstract: OBJECTIVE
  The activation of NF-κB signaling and unbalance of T-helper (Th) cells have been reported to play a key role in the pathogenesis of colitis. Cortex Phellodendri Chinensis (CPC) is commonly used to treat inflammation and diarrhea. Demethyleneberberine (DMB), a component of CPC, was reported to treat alcoholic liver disease as a novel natural mitochondria-targeted antioxidant in our previous study. In this study, we investigated whether DMB could protect against dextran sulfate sodium (DSS)-induced inflammatory colitis in mice by regulation of NF-κB pathway and Th cells homeostatis.
  
  
  METHODS
  Inflammatory colitis mice were induced by 3% DSS, and DMB were orally administered on the doses of 150 and 300 mg/kg. In vitro, DMB (10, 20, 40 μM) and N-acetyl cysteine (NAC, 5 mM) were co-cultured with RAW264.7 for 2 h prior to lipopolysaccharide (LPS) stimulation, and splenocytes from the mice were cultured ex vivo for 48 h for immune response test.
  
  
  RESULTS
  In vivo, DMB significantly alleviated the weight loss and diminished myeloperoxidase (MPO) activity, while significantly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and inhibited the activation of NF-κB signaling pathway. Furthermore, DMB decreased interferon (IFN)-γ, increased IL-4 concentration in the mice splenocytes and the ratio of IgG1/IgG2a in the serum. In vitro, ROS production and pro-inflammation cytokines were markedly inhibited by DMB in RAW264.7 cell.
  
  
  CONCLUSIONS
  Our findings revealed that DMB alleviated mice colitis and inhibited the inflammatory responses by inhibiting NF-κB pathway and regulating the balance of Th cells.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.|Department of Neurobiology and Anatomy, Northeast Ohio Medical University, Rootstown, OH, 44272, USA.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.
authors.forename: Rui-Yan
authors.initials: RY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.
authors.forename: Mei-Jing
authors.initials: MJ
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.
authors.forename: Ya-Xing
authors.initials: YX
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, China. ybzhang@cpu.edu.cn.
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D016264:Dextran Sulfate; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007074:Immunoglobulin G; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D001599:Berberine; C477155:demethyleneberberine; D016264:Dextran Sulfate
keywords: Colitis; DMB; NF-κB; Th cell