State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, PR China.
State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, PR China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 3):118892. doi: 10.1016/j.jep.2024.118892. Epub 2024 Oct 11.
Cimicifuga heracleifolia Kom. (C. heracleifolia) has demonstrated efficacy in treating gastrointestinal disorders, including splenasthenic diarrhea. Ulcerative colitis (UC), a chronic inflammatory bowel disease, shares similarities with splenasthenic diarrhea. However, the pharmacological effects of C. heracleifolia on UC and the underlying mechanisms remain unexplored.
The present study investigates the therapeutic potential and mechanisms of C. heracleifolia in UC.
Initially, network pharmacology analysis, encompassing ingredient screening, target prediction, protein-protein interaction (PPI) network analysis, and enrichment analysis, was employed to predict the mechanisms of C. heracleifolia. The findings were further validated using transcriptomics and functional assays in a dextran sulfate sodium (DSS)-induced UC model. Additionally, bioactive compounds were identified through surface plasmon resonance (SPR) analysis, molecular docking, and cell-based assays.
A total of 52 ingredients of C. heracleifolia were screened, and 32 key targets were identified within a PPI network comprising 285 potential therapeutic targets. Enrichment analysis indicated that the anti-UC effects of C. heracleifolia are mediated through immune response modulation and the inhibition of inflammatory signaling pathways. In vivo experiments showed that C. heracleifolia mitigated histological damage in the colon, reduced the expression of phosphorylated Akt1, nuclear factor-kappa B (NF-κB) p65, and inhibitor of Kappa B kinase α/β (IKKα/β), suppressed the content of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and enhanced the expression of tight junction proteins. Moreover, cimigenoside, caffeic acid, and methyl caffeate were identified as the bioactive constituents responsible for the UC treatment effects of C. heracleifolia.
In summary, this study is the first to demonstrate that C. heracleifolia exerts therapeutic effects on UC by enhancing the intestinal mucosal barrier and inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/NF-κB signaling pathway. These findings offer valuable insights into the clinical application of C. heracleifolia for UC management.
升麻属植物（C. heracleifolia）已被证明在治疗胃肠道疾病方面具有疗效，包括脾虚腹泻。溃疡性结肠炎（UC）是一种慢性炎症性肠病，与脾虚腹泻有相似之处。然而，升麻属植物（C. heracleifolia）对 UC 的药理作用及其潜在机制仍未得到探索。
本研究旨在探讨升麻属植物（C. heracleifolia）在 UC 中的治疗潜力及其机制。
首先，采用网络药理学分析方法，包括成分筛选、靶点预测、蛋白质-蛋白质相互作用（PPI）网络分析和富集分析，预测升麻属植物（C. heracleifolia）的作用机制。然后，通过葡聚糖硫酸钠（DSS）诱导的 UC 模型中的转录组学和功能测定进一步验证这些发现。此外，通过表面等离子体共振（SPR）分析、分子对接和基于细胞的测定鉴定生物活性化合物。
筛选出 52 种升麻属植物（C. heracleifolia）的成分，构建了包含 285 个潜在治疗靶点的 PPI 网络，确定了 32 个关键靶点。富集分析表明，升麻属植物（C. heracleifolia）的抗 UC 作用是通过调节免疫反应和抑制炎症信号通路来实现的。体内实验表明，升麻属植物（C. heracleifolia）减轻了结肠的组织损伤，降低了磷酸化 Akt1、核因子-κB（NF-κB）p65 和 IKKα/β 的表达，抑制了白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的含量，并增强了紧密连接蛋白的表达。此外，鉴定出毛蕊异黄酮苷、咖啡酸和甲基咖啡酸为升麻属植物（C. heracleifolia）治疗 UC 的生物活性成分。
综上所述，本研究首次证明，升麻属植物（C. heracleifolia）通过增强肠道黏膜屏障和抑制磷脂酰肌醇 3-激酶（PI3K）/AKT/NF-κB 信号通路发挥对 UC 的治疗作用。这些发现为升麻属植物（C. heracleifolia）在 UC 管理中的临床应用提供了有价值的见解。
