State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, China.
Sci Rep. 2024 Nov 30;14(1):29777. doi: 10.1038/s41598-024-77021-5.
In this study, we aimed to study the mechanism of costunolide (COS) and dehydrocostus lactone (DEH) in the treatment of ulcerative colitis (UC) based on network pharmacology, molecular docking and animal experiments. Firstly, network pharmacology was used to predict the target proteins of compounds and diseases. Subsequently, the network analysis was performed, and the key target proteins were screened out. Finally, molecular docking and animal experiments were conducted to validate the network pharmacology analysis results. A total of 39 common target proteins of compounds and diseases were collected. The target proteins TLR4, PIK3R1, PTGS2, RELA, NOS3, MPO and CHUK were obtained from PPI network analysis, GO analysis, KEGG enrichment analysis, and the compound-target-pathway network. Molecular docking results showed that COS and DEH could bind to these target proteins. The results of animal experiments showed that dextran sulfate sodium (DSS) induced UC in mice, resulting in weight loss, colon shortening, and significantly upregulated expression of TLR4, PIK3R1 and RELA in colon tissue. COS and DEH could reduce these pathological changes in UC mice. And they could alleviate UC by downregulating TLR4, PIK3R1 and RELA. Our findings suggested that COS and DEH could exert protective effects on UC by downregulating TLR4, PIK3R1, and RELA.
在这项研究中，我们旨在基于网络药理学、分子对接和动物实验研究木香烃内酯（COS）和去氢木香内酯（DEH）治疗溃疡性结肠炎（UC）的作用机制。首先，采用网络药理学预测化合物和疾病的靶蛋白。随后，进行网络分析，并筛选出关键靶蛋白。最后，进行分子对接和动物实验，验证网络药理学分析结果。共收集到化合物和疾病的 39 个共同靶蛋白。从 PPI 网络分析、GO 分析、KEGG 富集分析和化合物-靶标-通路网络中得到 TLR4、PIK3R1、PTGS2、RELA、NOS3、MPO 和 CHUK 等靶蛋白。分子对接结果表明，COS 和 DEH 可与这些靶蛋白结合。动物实验结果表明，葡聚糖硫酸钠（DSS）诱导小鼠 UC，导致体重减轻、结肠缩短，结肠组织中 TLR4、PIK3R1 和 RELA 的表达显著上调。COS 和 DEH 可减轻 UC 小鼠的这些病理变化。并通过下调 TLR4、PIK3R1 和 RELA 来缓解 UC。我们的研究结果表明，COS 和 DEH 通过下调 TLR4、PIK3R1 和 RELA 对 UC 发挥保护作用。
