Zhu Wenjing, Zhang Zhengjie, Wang Xinyuan
College of Art, Jiangsu Open University, Nanjing, China.
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Front Mol Biosci. 2025 Mar 21;12:1552360. doi: 10.3389/fmolb.2025.1552360. eCollection 2025.
Ulcerative colitis (UC) is a chronic and progressive inflammatory disease of the intestines, marked by recurrent inflammation along the digestive tract, leading to symptoms such as bloody diarrhea and weight loss, severely impacting patients' quality of life. Despite extensive research, current therapeutic treatment for UC still faces challenges in long-term efficacy and safety. Lanatoside C (LanC), as a type of cardiac glycosides, has shown promising anti-inflammatory effects. This study employs network pharmacology to investigate the effects and mechanisms of LanC in the treatment of UC.
LanC- and UC-associated target genes datasets were retrieved from the Genecards, DisGeNET, and Gene Expression Omnibus database. Integration analysis identified a common set of potential LanC targets for UC treatment. Analyses of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on these target genes. Additionally, a protein-protein interaction (PPI) network was constructed to identify the top targets with the highest connectivity. Molecular docking and cellular experiments were subsequently carried out to further validated these findings.
23 intersecting genes were identified as potential targets of LanC in UC. Among these, KDR, STAT3, ABCB1, CYP3A5, and CYP2B6 emerged as the top 5 targets with high therapeutic potential. Pathway analysis indicated the involvement of fatty acid and lipid metabolism, as well as xenobiotic metabolism pathways, which could be crucial for LanC's efficacy in treating UC. Molecular docking simulations revealed favorable binding interaction between LanC and KDR, STAT3, ABCB1, CYP3A5, and CYP2B6. Furthermore, experiments demonstrated that LanC significantly inhibits LPS-induced pro-inflammatory cytokines expression in RAW264.7 cells.
This study demonstrates a comprehensive overview of the therapeutic potential of LanC in UC and elucidates its mechanisms of action. These findings offer a theoretical basis for further optimizing UC clinical therapy and underscore the potential of LanC as a novel therapeutic option for UC.
溃疡性结肠炎（UC）是一种慢性进行性肠道炎症性疾病，其特征为沿消化道反复发生炎症，导致便血、腹泻和体重减轻等症状，严重影响患者的生活质量。尽管进行了广泛研究，但目前UC的治疗方法在长期疗效和安全性方面仍面临挑战。毛花苷C（LanC）作为一种强心苷，已显示出有前景的抗炎作用。本研究采用网络药理学方法探讨LanC治疗UC的作用及机制。
从Genecards、DisGeNET和基因表达综合数据库中检索LanC和UC相关的靶基因数据集。整合分析确定了一组用于UC治疗的潜在LanC共同靶标。对这些靶基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。此外，构建蛋白质-蛋白质相互作用（PPI）网络以确定连接性最高的前几个靶标。随后进行分子对接和细胞实验以进一步验证这些发现。
确定了23个交叉基因作为LanC在UC中的潜在靶标。其中，激酶插入域受体（KDR）、信号转导和转录激活因子3（STAT3）、ATP结合盒转运蛋白B1（ABCB1）、细胞色素P450 3A5（CYP3A5）和细胞色素P450 2B6（CYP2B6）成为具有高治疗潜力的前5个靶标。通路分析表明脂肪酸和脂质代谢以及外源性物质代谢通路参与其中，这可能对LanC治疗UC的疗效至关重要。分子对接模拟显示LanC与KDR、STAT3、ABCB1、CYP3A5和CYP2B6之间存在良好的结合相互作用。此外，实验表明LanC显著抑制脂多糖（LPS）诱导的RAW264.7细胞中促炎细胞因子的表达。
本研究全面概述了LanC在UC中的治疗潜力并阐明了其作用机制。这些发现为进一步优化UC临床治疗提供了理论依据，并强调了LanC作为UC新型治疗选择的潜力。
