Abstract
PURPOSE: To investigate the therapeutic effect of Tripterygium wilfordii polyglycoside (TWP), a derivative from a Chinese traditional herb, on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, in a model for inflammatory bowel disease (IBD) in rats. METHODS: TWP was administrated to Wistar rats during TNBS-induced colitis to determine its therapeutic effect on active inflammation using the Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), flow cytometry, and Western blotting. Peripheral blood CD4(+) T-cells were isolated from patients with ulcerative colitis (UC) and incubated with TWP to verify its immune regulation mechanism by qRT-PCR and flow cytometry. RESULTS: Intragastric administration of TWP attenuated the severity of intestinal inflammation in TNBS-induced rat colitis, characterized by decreased DAI, histopathological scores, and expression of IL-6, TNFα, IFNγ, and IL-17A in intestinal mucosa. Furthermore, TWP reduced IL-17A(+)CD4(+) T-cells, while enhanced Foxp3(+)CD25(+)CD4(+) T-cells in peripheral blood, mesenteric lymph nodes (MLN), and spleen in rat colitis. Downstream signaling including ROR-γt, STAT3, and HIF1α expression in intestinal mucosa were suppressed by TWP. In addition, incubation with TWP suppressed IL-17A(+)CD4(+) T-cell differentiation, while it promoted Foxp3(+)CD25(+)CD4(+) T-cell differentiation in CD4(+) T-cells isolated from UC patients. CONCLUSION: TWP successfully ameliorated experimental rat colitis via regulating innate immune responses as well as Th17/Treg balance in intestinal mucosa, peripheral blood, MLN, and spleen. Moreover, the differentiation of peripheral blood CD4(+) T-cell isolated from patients with UC was modulated by TWP. TWP may act as an optional complementary and alternative medicine for IBD.