Zhang Cui, Ju Jingyi, Wu Xiaohan, Yang Jiaolan, Yang Qinglu, Liu Changqin, Chen Liang, Sun Xiaomin
Gastroenterology Department, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, People's Republic of China.
Gastroenterology Department, The Shanghai Tenth People's Hospital, Chongming Branch, Shanghai, People's Republic of China.
J Inflamm Res. 2021 Apr 1;14:1243-1255. doi: 10.2147/JIR.S293961. eCollection 2021.
To investigate the therapeutic effect of 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.
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.
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-17ACD4 T-cells, while enhanced Foxp3CD25CD4 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-17ACD4 T-cell differentiation, while it promoted Foxp3CD25CD4 T-cell differentiation in CD4 T-cells isolated from UC patients.
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.
在大鼠炎症性肠病（IBD）模型中，研究中药提取物多苷（TWP）对2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎的治疗效果。
在TNBS诱导的结肠炎期间，对Wistar大鼠给予TWP，通过定量实时聚合酶链反应（qRT-PCR）、流式细胞术和蛋白质免疫印迹法，确定其对活动性炎症的治疗效果。从溃疡性结肠炎（UC）患者中分离外周血CD4 T细胞，并用TWP孵育，通过qRT-PCR和流式细胞术验证其免疫调节机制。
胃内给予TWP可减轻TNBS诱导的大鼠结肠炎的肠道炎症严重程度，表现为疾病活动指数（DAI）降低、组织病理学评分降低以及肠黏膜中白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）、干扰素γ（IFNγ）和白细胞介素-17A（IL-17A）表达降低。此外，TWP可减少大鼠结肠炎外周血、肠系膜淋巴结（MLN）和脾脏中IL-17A+CD4 T细胞，同时增加叉头框蛋白3（Foxp3）+CD25+CD4 T细胞。TWP抑制肠黏膜中包括维甲酸相关孤儿受体γt（ROR-γt）、信号转导子和转录激活子3（STAT3）以及缺氧诱导因子1α（HIF1α）表达在内的下游信号传导。此外，用TWP孵育可抑制从UC患者分离的CD4 T细胞中IL-17A+CD4 T细胞分化，同时促进Foxp3+CD25+CD4 T细胞分化。
TWP通过调节肠黏膜、外周血、MLN和脾脏中的固有免疫反应以及Th17/调节性T细胞（Treg）平衡，成功改善了实验性大鼠结肠炎。此外，TWP调节了从UC患者分离的外周血CD4 T细胞的分化。TWP可能是IBD的一种可选补充和替代药物。
