Huang Xiaoyan, Li Liqun, Zheng Chaowei, Li Jianfeng, Chen Guangwen, Chen Yalu
Department of Gastroenterology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning City, Guangxi Zhuang Autonomous Region, People's Republic of China.
J Inflamm Res. 2024 Aug 5;17:5235-5249. doi: 10.2147/JIR.S472812. eCollection 2024.
Ulcerative colitis (UC), a highly relapsing non-specific disease, is difficult to cure completely. The investigation aims to determine the protective effect and potential action mechanism of Xuanbi yuyang decoction (XBD) on UC.
The chemical composition of XBD was determined through non-targeted metabolomics analysis. Subsequently, experimental mice were orally given 3% DSS for 6 days, followed by XBD treatment (0.3 mL, 0.4 mL). In vitro, the human colon epithelial cells were co-treated with DSS and medicated serum. The therapeutic effects of XBD on UC were evaluated in vivo and vitro. The mechanisms of XBD against UC were determined by detecting hallmarks related to pyroptosis and Interleukin (IL)-17 pathways using Western blot and ELISA. The recombinant human interleukin 17A (rhIL17A) and was applied for further verifying the effect of XBD on IL-17 pathway in UC cells.
XBD supplementation restored DSS-induced weight loss, colon shortening and tissue damage, and reduced DAI. Moreover, XBD enhanced viability, repaired the intestinal mucosal barrier of colitis, decreased pro-inflammatory cytokines levels, and inhibited pyroptosis. Additionally, DSS increased the expression of IL-17 pathway was and cytokines (IL-17A, IL-6), which were blocked by XBD treatment. The rhIL17A treatment attenuated protective effect against DSS-induced colitis and could also enhance pyroptosis.
XBD has a favorable protective effect against DSS-induced colitis through restraining pyroptosis via inhibition of IL-17 signaling pathway activation, suggesting XBD may be a new and effective treatment therapy for UC.
溃疡性结肠炎（UC）是一种极易复发的非特异性疾病，难以完全治愈。本研究旨在确定宣痹愈疡汤（XBD）对UC的保护作用及潜在作用机制。
通过非靶向代谢组学分析确定XBD的化学成分。随后，给实验小鼠口服3%葡聚糖硫酸钠（DSS）6天，之后进行XBD治疗（0.3 mL、0.4 mL）。在体外，将人结肠上皮细胞与DSS和含药血清共同处理。在体内和体外评估XBD对UC的治疗效果。通过蛋白质免疫印迹法（Western blot）和酶联免疫吸附测定法（ELISA）检测与细胞焦亡和白细胞介素（IL）-17途径相关的标志物，确定XBD抗UC的作用机制。应用重组人白细胞介素17A（rhIL17A）进一步验证XBD对UC细胞中IL-17途径的作用。
补充XBD可恢复DSS诱导的体重减轻、结肠缩短和组织损伤，并降低疾病活动指数（DAI）。此外，XBD可提高细胞活力，修复结肠炎的肠黏膜屏障，降低促炎细胞因子水平，并抑制细胞焦亡。另外，DSS增加了IL-17途径相关细胞因子（IL-17A、IL-6）的表达，而XBD治疗可阻断这种增加。rhIL17A治疗减弱了对DSS诱导的结肠炎的保护作用，还可增强细胞焦亡。
XBD通过抑制IL-17信号通路激活来抑制细胞焦亡，从而对DSS诱导的结肠炎具有良好的保护作用，提示XBD可能是一种治疗UC的新型有效疗法。
