Zhang Shixiong, Wang Yuhua, Ren Xuetong, Chen Haoyu, Gao Tianyu, Liu Yang, Lu Lishan, Ma Junzhuo, Bai Haiyan, Wang Yangang
Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People's Republic of China.
The First Affiliated Hospital of Hebei University of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People's Republic of China.
J Inflamm Res. 2025 Sep 4;18:12245-12261. doi: 10.2147/JIR.S533936. eCollection 2025.
Xianglian Anchang Decoction (XLAC) shows significant promise in treating ulcerative colitis (UC) based on clinical experience. However, the specific mechanism of XLAC treatment for UC is still not well understood.
This study aims to explore the pharmacological mechanism of XLAC in treating UC through network pharmacology and experimental verification.
In this study, DSS-induced UC mouse model was established to evaluate the effects of XLAC on body weight, Disease Activity Index scores, spleen index, and colon length. Pathological change and intestinal barrier integrity were analyzed via hematoxylin-eosin, periodic acid-Schiff staining, immunofluorescence, RT-qPCR, Western blot, and ELISA. Network pharmacology and bioinformatics analyses were employed to predict potential targets of XLAC, followed by molecular docking to validate the binding affinity between key components and TLR4.
XLAC significantly ameliorated weight loss, colon shortening, and splenomegaly in UC mice ( < 0.001), restored intestinal barrier integrity, and increased the expression of tight junction proteins (ZO-1/Occludin) and goblet cell numbers. Network pharmacology identified TLR4 as a key target, and molecular docking demonstrated strong binding affinity (Vina score < -5) between XLAC active components (eg, trans-4-coumaric acid, methyl cinnamate) and TLR4. In vivo experiments confirmed that XLAC downregulated the protein levels of TLR4, NLRP3, and GSDMD-N, as well as the mRNA expression of IL-1β and IL-18 ( < 0.05), thereby suppressing pyroptosis.
XLAC alleviates UC inflammation and intestinal barrier damage by targeting TLR4 to inhibit NLRP3 inflammasome activation and GSDMD-mediated pyroptosis. This study provides mechanistic insights into the clinical efficacy of XLAC for UC treatment.
基于临床经验，香连安肠汤（XLAC）在治疗溃疡性结肠炎（UC）方面显示出显著前景。然而，XLAC治疗UC的具体机制仍未完全明确。
本研究旨在通过网络药理学和实验验证探索XLAC治疗UC的药理机制。
本研究建立了葡聚糖硫酸钠（DSS）诱导的UC小鼠模型，以评估XLAC对体重、疾病活动指数评分、脾脏指数和结肠长度的影响。通过苏木精-伊红染色、过碘酸-希夫染色、免疫荧光、实时定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法（Western blot）和酶联免疫吸附测定（ELISA）分析病理变化和肠道屏障完整性。采用网络药理学和生物信息学分析预测XLAC的潜在靶点，随后进行分子对接以验证关键成分与Toll样受体4（TLR4）之间的结合亲和力。
XLAC显著改善了UC小鼠的体重减轻、结肠缩短和脾肿大（<0.001），恢复了肠道屏障完整性，并增加了紧密连接蛋白（闭合蛋白/闭合小环蛋白）的表达和杯状细胞数量。网络药理学确定TLR4为关键靶点，分子对接证明XLAC活性成分（如反式对香豆酸、肉桂酸甲酯）与TLR4之间具有很强的结合亲和力（Vina评分<-5）。体内实验证实，XLAC下调了TLR4、NOD样受体蛋白3（NLRP3）和Gasdermin D-N（GSDMD-N）的蛋白水平，以及白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的mRNA表达（<0.05），从而抑制细胞焦亡。
XLAC通过靶向TLR4抑制NLRP3炎性小体激活和GSDMD介导的细胞焦亡，减轻UC炎症和肠道屏障损伤。本研究为XLAC治疗UC的临床疗效提供了机制性见解。
