Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
The First Clinical College, Hubei University of Chinese Medicine, Wuhan, 430065, China; Department of Gerontology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, 430022, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 3):118885. doi: 10.1016/j.jep.2024.118885. Epub 2024 Oct 5.
Compound sophora decoction (CSD), a widely used Chinese herbal formula, has been shown to effectively alleviate symptoms ulcerative colitis (UC), including of bloody diarrhea, tenesmus, abdominal pain, and fever. Despite its clinical use, the precise pharmacological mechanisms of CSD remain enigmatic.
This study aims to investigate the potential efficacy and underlying mechanisms of CSD in the treatment of UC by employing an integrative pharmacology-based approach, molecular docking analysis and experimental validation.
In this study, an integrative pharmacology-based approach was employed to predict the primary pathway through which CSD treats UC. The mechanism of CSD was further validated using a DSS-induced UC mouse model. Disease severity was assessed by monitoring stool property, body weight, colon length, and colon histopathology. Colonic pathological changes were examined using hematoxylin and eosin (HE) staining. The concentration of cytokines was measured via ELISA, while key molecules in the PI3K-AKT pathway and autophagy-related markers were evaluated using Western blotting. Autophagy in intestinal epithelial cells was observed using electron microscopy.
The results demonstrated that CSD alleviated DSS-induced UC by inhibiting the activation of PI3K-AKT pathway, reducing the release of inflammatory cytokines, down-regulating oxidative mediators, and enhancing autophagy. Moreover, the protective effects of CSD were diminished by bpV, a PTEN inhibitor, further supporting the involvement of the PI3K-AKT pathway.
The underlying mechanism of CSD's therapeutic effect on UC may involve significant attenuation of DSS-induced intestinal inflammation by promoting autophagy through the inhibition of PI3K-AKT pathway activation.
复方苦参汤（CSD）是一种广泛应用的中药方剂，已被证明能有效缓解溃疡性结肠炎（UC）的症状，包括血性腹泻、里急后重、腹痛和发热。尽管已在临床上应用，但 CSD 的确切药理机制仍不清楚。
本研究旨在采用基于整合药理学的方法、分子对接分析和实验验证，研究 CSD 治疗 UC 的潜在疗效和潜在机制。
在这项研究中，采用基于整合药理学的方法预测 CSD 治疗 UC 的主要途径。采用 DSS 诱导的 UC 小鼠模型进一步验证 CSD 的作用机制。通过监测粪便特性、体重、结肠长度和结肠组织病理学来评估疾病严重程度。采用苏木精和伊红（HE）染色检查结肠的病理变化。通过 ELISA 测量细胞因子的浓度，通过 Western blot 评估 PI3K-AKT 通路和自噬相关标志物中的关键分子。通过电子显微镜观察肠上皮细胞中的自噬。
结果表明，CSD 通过抑制 PI3K-AKT 通路的激活、减少炎症细胞因子的释放、下调氧化介质以及增强自噬来缓解 DSS 诱导的 UC。此外，PTEN 抑制剂 bpV 削弱了 CSD 的保护作用，进一步支持 PI3K-AKT 通路的参与。
CSD 治疗 UC 的疗效的潜在机制可能涉及通过抑制 PI3K-AKT 通路的激活来促进自噬，从而显著减轻 DSS 诱导的肠道炎症。
