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

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.

Efficacy and Safety of Tripterygium Wilfordii Glycoside Tablets Combined with Acitretin Capsules in the Treatment of Moderate to Severe Plaque Psoriasis: A Randomized Controlled Trial

“…Previous studies have shown that acitretin inhibits Th17 cell differentiation through the retinoic acid-related receptor RORγt, a key transcription factor for Th17 cell development [24]. Zhang et al came to the conclusion that TWGs inhibited Th17 cell differentiation by inhibiting RORC and STAT3 expression, while promoting Treg cell differentiation 5 Applied Bionics and Biomechanics by enhancing the Foxp3 expression in CD4 + T cells [25]. Besides, TWGs can also act on HIF1α to regulate the balance of Th17/Treg [26].…”

Traditional Chinese Medicine and Natural Products: Potential Approaches for Inflammatory Bowel Disease

“…In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mice, Treg levels were significantly increased by Astragalus aaronii (Eig) Zohary polysaccharide ( Zhao et al, 2016 ). Oxymatrine extracted from the roots of Sophora flavescens Aiton, the ingredient edible bird’s nest and Tripterygium wilfordii polyglycoside were able to regulate Th17/Treg balance and have a protective effect against colitis ( Wang Y. et al, 2019 ; Song et al, 2019 ; Fan et al, 2021 ; Zhang et al, 2021 ). In addition, botanical drugs Portulaca oleracea L., Ripened Pu-erh tea, and Fagopyrum cymosum (Trevir.)…”

Traditional Chinese Medicine Regulates Th17/Treg Balance in Treating Inflammatory Bowel Disease

“…An active ingredient derived from Tripterygium wilfordii Hook F., Tripterygium wilfordii polyglycoside, possesses antitumor, immunomodulatory, and other pharmacological properties [ 45 , 46 ]. Tripterygium wilfordii polyglycoside was found to inhibit Th17 cells differentiation by downregulating RORC and STAT3 expression, while IL-17 production upregulated Foxp3 and promoted Treg cells formation, further regulating Th17/Treg balance and inhibiting intestinal inflammation in colitic mice [ 47 ]. Baicalein is a flavonoid bioactive component derived from Scutellaria baicalensis , and its pharmacological effects, such as antibacterial, neuroprotective, and antitumor, have been demonstrated in a variety of disease models [ 48 , 49 ].…”