Background

Restoring immune homeostasis by targeting the Th17/Treg response is a potentially valuable therapeutic strategy for ulcerative colitis (UC). Astragaloside IV (AS-Ⅳ) is a phytochemical naturally occurring in Astragalus membranaceus that has good anti-inflammatory, anti-oxidant and anti-stress properties. However, the effects of AS-IV on the homeostasis of Th17/Treg cells in colitis mice remains unknown.

Purpose

To investigate the protective effects and potential immunomodulatory mechanisms of AS-IV on UC.

Methods

This study was constructed for DSS-induced acute colitis and recurrent colitis, with AS-IV administered prophylactically and therapeutically, respectively. The balance of Th17/Treg cells was analyzed by flow cytometry, their specific nuclear transcription factors were detected by RT-PCR as well as their secreted inflammatory cytokines were detected by ELISA and RT-PCR. Notch signaling-related proteins were detected by RT-PCR and Western blotting. Oxidative stress indicators were measured by biochemical technology.

Results

In this study, AS-IV treatment not only effectively prevented and alleviated the clinical symptoms of DSS-induced colitis mice, including weight loss, DAI soaring, colon length shortening and colon weight gain, but also significantly improved ulcer formation, inflammatory cell infiltration and index, and regulated the expression of inflammatory cytokines in colon tissues. Importantly, the efficacy of high-dose AS-IV (100 mg/kg/day) in mice with recurrent colitis in this study was comparable to that of 5-ASA. AS-IV early administration was able to reshape the homeostasis of Th17/Treg cells in mice with acute colitis; meanwhile, AS-IV inhibited Th17 cell responses and promoted Treg cell responses in mice with recurrent colitis. Moreover, AS-IV not only inhibited the activation of Notch signaling pathway in colitis mice, but also prevented and ameliorated DSS-induced oxidative stress injury.

Conclusion

In conclusion, AS-IV effectively prevented and alleviated UC by reshaping Th17/Treg cell homeostasis and anti-oxidative stress.

中文翻译：

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黄芪甲苷通过调节Th17/Treg细胞平衡缓解溃疡性结肠炎

背景

通过靶向 Th17/Treg 反应来恢复免疫稳态是溃疡性结肠炎 (UC) 的一种潜在有价值的治疗策略。黄芪甲苷 (AS-IV) 是一种天然存在于黄芪中的植物化学物质，具有良好的抗炎、抗氧化和抗应激特性。然而，AS-IV 对结肠炎小鼠 Th17/Treg 细胞稳态的影响仍然未知。

目的

探讨AS-IV对UC的保护作用和潜在的免疫调节机制。

方法

本研究针对 DSS 诱导的急性结肠炎和复发性结肠炎而构建，分别以预防性和治疗性方式施用 AS-IV。流式细胞仪分析Th17/Treg细胞平衡，RT-PCR检测其特异性核转录因子，ELISA和RT-PCR检测其分泌的炎性细胞因子。通过RT-PCR和Western印迹检测Notch信号相关蛋白。氧化应激指标采用生化技术测定。

结果

在本研究中，AS-IV 治疗不仅有效预防和缓解了 DSS 诱导的结肠炎小鼠的临床症状，包括体重减轻、DAI 飙升、结肠长度缩短和结肠重量增加，而且显着改善了溃疡形成、炎症细胞浸润和指数，并调节结肠组织中炎性细胞因子的表达。重要的是，本研究中高剂量 AS-IV（100 mg/kg/天）对复发性结肠炎小鼠的疗效与 5-ASA 相当。AS-IV 早期给药能够重塑急性结肠炎小鼠体内 Th17/Treg 细胞的稳态；同时，AS-IV 在复发性结肠炎小鼠中抑制 Th17 细胞反应并促进 Treg 细胞反应。此外，AS-IV 不仅抑制结肠炎小鼠 Notch 信号通路的激活，

结论

总之，AS-IV 通过重塑 Th17/Treg 细胞稳态和抗氧化应激有效预防和缓解 UC。