Formula-Pattern Research Center, Jiangxi University of Traditional Chinese Medicine, 1688 Meiling Road, Nanchang, Jiangxi 330004, China; Laboratory Animal Research Center for Science and Technology, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, Jiangxi 330004, China.
Phytomedicine. 2022 Sep;104:154287. doi: 10.1016/j.phymed.2022.154287. Epub 2022 Jun 19.
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.
To investigate the protective effects and potential immunomodulatory mechanisms of AS-IV on UC.
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.
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.
In conclusion, AS-IV effectively prevented and alleviated UC by reshaping Th17/Treg cell homeostasis and anti-oxidative stress.
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 细胞稳态的影响尚不清楚。
探讨 AS-Ⅳ 对 UC 的保护作用及潜在的免疫调节机制。
本研究构建了 DSS 诱导的急性结肠炎和复发性结肠炎模型，分别采用 AS-Ⅳ 进行预防和治疗。通过流式细胞术分析 Th17/Treg 细胞的平衡，通过 RT-PCR 检测其特定的核转录因子，通过 ELISA 和 RT-PCR 检测其分泌的炎症细胞因子。通过 RT-PCR 和 Western blot 检测 Notch 信号相关蛋白。通过生化技术检测氧化应激指标。
本研究中，AS-Ⅳ 治疗不仅能有效预防和缓解 DSS 诱导的结肠炎小鼠的临床症状，包括体重减轻、DAI 飙升、结肠缩短和结肠重量增加，还能显著改善溃疡形成、炎症细胞浸润和指数，并调节结肠组织中炎症细胞因子的表达。重要的是，本研究中复发性结肠炎小鼠高剂量 AS-Ⅳ（100mg/kg/天）的疗效与 5-ASA 相当。AS-Ⅳ 早期给药可重塑急性结肠炎小鼠 Th17/Treg 细胞的稳态；同时，AS-Ⅳ 抑制复发性结肠炎小鼠 Th17 细胞反应，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，还能预防和改善 DSS 诱导的氧化应激损伤。
综上所述，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。
