Oridonin derivative ameliorates experimental colitis by inhibiting activated T-cells and translocation of nuclear factor-kappa B

ObjectiveTo 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. MethodsColitis 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)-, interferon (IFN)- and interleukin (IL)-17A, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-B) in the colonic tissues were evaluated. The effect of HAO472 on NF-B signaling pathway in lymphocytes was also invesigated. ResultsHAO472 significantly ameliorated the clinical symptoms, reduced the severity of the inflammation and decreased mortality in the mouse model. HAO472 also reduced TNF-, IFN-, IL-17A, iNOS/COX-2 and lymphocyte proliferation. These changes were associated with a significant decrease in NF-B p65 expression and activity. ConclusionHAO472 has positive effects on TNBS-induced colitis by modulating the subsets and functions of lymphocytes, suppressing inflammation and inhibiting the nuclear translocation of NF-B p65 subunits.