Institute of Traditional Chinese Medicine and Stem Cell Research, College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China.
J Ethnopharmacol. 2023 Dec 5;317:116847. doi: 10.1016/j.jep.2023.116847. Epub 2023 Jun 24.
Si-Wu Decoction (SWD) is a traditional Chinese medicine decoction. SWD is commonly used to treat blood deficiency syndrome. It is also used to treat some ulcerative colitis (UC) patients now, but the mechanism of action remains unclear.
This study explored the efficacy and mechanism of action of SWD in treating UC based on network pharmacology and related experimental validation.
Several databases were used to screen SWD for major active ingredients, targets of the ingredients, and UC disease genes. Cytoscape 3.8.2 software was used for topological analysis to construct the drug-compound-disease gene-target relationship network. The String database platform was used to construct the target protein interaction network. The DAVID (Database for Annotation, Visualization and Integrated Discovery) database was used to perform the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for the key targets. DSS (Dextran Sulfate Sodium)-induced UC mouse model was used to evaluate the in-vivo activity of SWD. Western Blot analysis and quantitative polymerase chain reaction were performed to verify the targets in the related pathways.
Network pharmacology revealed that the SWD targeted pathway network involved 12 core targets and 15 major pathways. SWD may play a part by targeting key targets such as nuclear factor-kappaB (NF-κB), Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) pathway, and several mitogenic pathways. We showed that SWD largely restored the colorectal structure in UC model mice. Compared to the model group, the SWD group showed reduced infiltration of inflammatory cells. SWD significantly decreased the mRNA levels of IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor-alpha), IL-1b (Interleukin-1beta) and other pro-inflammatory factors. Western Blot results showed that SWD concentration-dependently inhibited STAT3 and NF-κB activation in DSS-treated colon tissue.
Our findings suggest that SWD treats UC by inhibiting STAT3 and NF-κB signaling pathways, reducing the expression of inflammatory cytokines, and improving epithelial repair in experimental colitis, thus shedding light on the mechanisms by which SWD exerts its effects on UC.
四物汤（SWD）是一种中药方剂。SWD 通常用于治疗血虚证。现在也用于治疗一些溃疡性结肠炎（UC）患者，但作用机制尚不清楚。
本研究基于网络药理学和相关实验验证，探讨 SWD 治疗 UC 的疗效和作用机制。
利用多个数据库筛选 SWD 的主要活性成分、成分靶点和 UC 疾病基因。使用 Cytoscape 3.8.2 软件进行拓扑分析，构建药物-化合物-疾病基因-靶点关系网络。利用 String 数据库平台构建靶点蛋白互作网络。利用 DAVID（数据库注释、可视化和综合发现）数据库对关键靶点进行 GO（基因本体论）和 KEGG（京都基因与基因组百科全书）富集分析。采用葡聚糖硫酸钠（DSS）诱导 UC 小鼠模型评价 SWD 的体内活性。采用 Western Blot 分析和实时定量聚合酶链反应验证相关通路中的靶点。
网络药理学显示，SWD 靶向通路网络涉及 12 个核心靶点和 15 条主要通路。SWD 可能通过靶向关键靶点如核因子-κB（NF-κB）、Janus 激酶（JAK）-信号转导和转录激活因子 3（STAT3）通路以及几种有丝分裂途径发挥作用。我们发现，SWD 可在很大程度上恢复 UC 模型小鼠的结直肠结构。与模型组相比，SWD 组炎症细胞浸润减少。SWD 显著降低了 UC 模型小鼠结肠组织中 IL-6（白细胞介素-6）、TNF-α（肿瘤坏死因子-α）、IL-1b（白细胞介素-1β）等促炎因子的 mRNA 水平。Western Blot 结果表明，SWD 浓度依赖性地抑制了 DSS 处理的结肠组织中 STAT3 和 NF-κB 的激活。
本研究结果提示，SWD 通过抑制 STAT3 和 NF-κB 信号通路，降低促炎细胞因子的表达，改善实验性结肠炎中的上皮修复，从而为 SWD 治疗 UC 的作用机制提供了新的见解。
