Tripterygium wilfordii Polyglycoside Ameliorated TNBS-Induced Colitis in Rats via Regulating Th17/Treg Balance in Intestinal Mucosa

Abstract

Cui Zhang,1 Jingyi Ju,1 Xiaohan Wu,1 Jiaolan Yang,1 Qinglu Yang,1 Changqin Liu,1 Liang Chen,1 Xiaomin Sun1,2 1Gastroenterology Department, The Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China; 2Gastroenterology Department, The Shanghai Tenth People’s Hospital, Chongming Branch, Shanghai, People’s Republic of ChinaCorrespondence: Xiaomin SunThe Shanghai Tenth People’s Hospital, Tongji University, Yanchang Middle Road No. 301, Shanghai, People’s Republic of ChinaTel [phone]Email [email protected]: 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.Keywords: inflammatory bowel disease, Tripterygium wilfordii polyglycoside, intestinal mucosa immunity, T helper 17 cell, regulatory T-cell

Keywords

• inflammatory bowel disease
• tripterygium wilfordii polyglycoside
• intestinal mucosa immunity
• t helper 17 cell
• regulatory t cell