Zhang Yannan, Zhang Shuai, Fan Yimeng, Huang Sijuan, Wang Shimin, Hao Zhihui, Shen Jianzhong
National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China.
Pharmaceuticals (Basel). 2025 Jan 16;18(1):109. doi: 10.3390/ph18010109.
: Cold-dampness diarrhea (CDD) is a common gastrointestinal disorder in children, characterized by diarrhea and intestinal barrier dysfunction. Weiling decoction (WLD) is frequently used in clinical practice to treat CDD, a condition triggered by multiple factors. However, the molecular mechanisms underlying its therapeutic effects remain poorly understood. : This study aimed to evaluate the efficacy of WLD in treating CDD and to elucidate its potential mechanisms. : UPLC-HRMS/MS was employed to identify the chemical constituents of WLD and the absorption components in the plasma of WLD-treated rats. Additionally, a rat model of CDD was established to assess the therapeutic effects of WLD through a comprehensive approach. To elucidate the molecular mechanisms underlying these effects, network pharmacology and transcriptomic analyses were performed to identify potential signaling pathways associated with CDD alleviation. Molecular docking and flow cytometry assays were subsequently utilized to validate the identified signaling pathways. : A total of 223 chemical components were detected in WLD, and 49 absorption components were identified in the plasma of WLD-treated rats by UPLC-HRMS/MS. WLD treatment significantly alleviated the symptoms of CDD, reduced intestinal damage, and diminished the inflammatory response. Additionally, WLD influenced key genes in immune-related pathways. Molecular docking revealed strong binding affinities between the main components of WLD and key targets within these pathways. Flow cytometry, along with the analysis of inflammatory cytokines and transcription factors, demonstrated that WLD modulated the balance between Th1/Th2 and Th17/Treg cell populations. : This study provides the first evidence that WLD alleviates CDD by regulating the balance between Th1/Th2 and Th17/Treg cell populations. These findings offer a theoretical basis for future investigations into the therapeutic potential of WLD in the treatment of CDD.
寒湿泄泻（CDD）是儿童常见的胃肠道疾病，其特征为腹泻和肠道屏障功能障碍。萎苓汤（WLD）在临床实践中常用于治疗由多种因素引发的CDD。然而，其治疗效果的分子机制仍知之甚少。
本研究旨在评估WLD治疗CDD的疗效并阐明其潜在机制。
采用超高效液相色谱-高分辨质谱联用技术（UPLC-HRMS/MS）鉴定WLD的化学成分以及WLD处理大鼠血浆中的吸收成分。此外，建立CDD大鼠模型，通过综合方法评估WLD的治疗效果。为阐明这些作用的分子机制，进行网络药理学和转录组分析以确定与CDD缓解相关的潜在信号通路。随后利用分子对接和流式细胞术试验验证所确定的信号通路。
通过UPLC-HRMS/MS在WLD中总共检测到223种化学成分，在WLD处理大鼠的血浆中鉴定出49种吸收成分。WLD治疗显著减轻了CDD的症状，减少了肠道损伤，并减轻了炎症反应。此外，WLD影响免疫相关通路中的关键基因。分子对接显示WLD的主要成分与这些通路中的关键靶点之间具有很强的结合亲和力。流式细胞术以及对炎性细胞因子和转录因子的分析表明，WLD调节了Th1/Th2和Th17/Treg细胞群体之间的平衡。
本研究首次提供证据表明，WLD通过调节Th1/Th2和Th17/Treg细胞群体之间的平衡来缓解CDD。这些发现为未来研究WLD治疗CDD的治疗潜力提供了理论基础。
