title: Oridonin derivative ameliorates experimental colitis by inhibiting activated T-cells and translocation of nuclear factor-kappa B.
abstract: OBJECTIVE
  To confirm the potential therapeutic efficacy of HAO472 against inflammatory bowel disease (IBD), we investigated the modulatory functions of HAO472 in a mouse model of trinitrobenzene sulfonic acid (TNBS)-induced colitis.
  
  
  METHODS
  Colitis was induced via an intrarectal injection of TNBS in mice. HAO472 (5.0 mg/kg or 7.5 mg/kg) or 1 mg/kg dexamethasone (DX) was injected intraperitoneally into the mice after the TNBS administration. Behavioral and weight changes, macroscopic and histological assessments of colon, the expressions of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-17A, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) in the colonic tissues were evaluated. The effect of HAO472 on NF-κB signaling pathway in lymphocytes was also invesigated.
  
  
  RESULTS
  HAO472 significantly ameliorated the clinical symptoms, reduced the severity of the inflammation and decreased mortality in the mouse model. HAO472 also reduced TNF-α, IFN-γ, IL-17A, iNOS/COX-2 and lymphocyte proliferation. These changes were associated with a significant decrease in NF-κB p65 expression and activity.
  
  
  CONCLUSIONS
  HAO472 has positive effects on TNBS-induced colitis by modulating the subsets and functions of lymphocytes, suppressing inflammation and inhibiting the nuclear translocation of NF-κB p65 subunits.
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hai Li
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Shu Bei
authors.initials: SB
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yun Wei
authors.initials: YW
authors.lastname: Sun
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D045786:Diterpenes, Kaurane / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D045786:Diterpenes, Kaurane; D005765:Gastrointestinal Agents; C000613319:HAO472; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014302:Trinitrobenzenesulfonic Acid; D000409:Alanine
keywords: NF-kappa B; animal models; cytokines; inflammatory bowel diseases; lymphocytes; oridonin