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Oridonin derivative ameliorates experimental colitis by inhibiting activated T‐cells and translocation of nuclear factor‐kappa B
Author(s) -
Liu Qian Qian,
Wang Hai Li,
Chen Ke,
Wang Shu Bei,
Xu Ying,
Ye Qiao,
Sun Yun Wei
Publication year - 2016
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/1751-2980.12314
Subject(s) - colitis , nitric oxide synthase , medicine , tumor necrosis factor alpha , inflammatory bowel disease , inflammation , pharmacology , dexamethasone , nf κb , nitric oxide , interleukin , immunology , cytokine , disease
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. Conclusion 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.