Data Sheet 1_Network pharmacology analysis of Lanatoside C: molecular targets and mechanisms in the treatment of ulcerative colitis.csv

IntroductionUlcerative 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.
MethodLanC- 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.
Results23 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, In vitro experiments demonstrated that LanC significantly inhibits LPS-induced pro-inflammatory cytokines expression in RAW264.7 cells.
ConclusionThis 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.

引言 溃疡性结肠炎（Ulcerative colitis, UC）是一类慢性进展性肠道炎症性疾病，以消化道反复炎症为核心特征，可引发血性腹泻、体重下降等临床症状，严重降低患者生活质量。尽管学界已开展大量研究，当前UC的临床治疗仍面临长期疗效与安全性不足的双重挑战。毛花苷C（Lanatoside C, LanC）属于强心苷类化合物，既往研究已证实其具有可观的抗炎活性。本研究采用网络药理学方法，系统探究LanC治疗UC的作用效果与分子机制。
方法 从GeneCards、DisGeNET及基因表达综合数据库（Gene Expression Omnibus, GEO）中检索LanC与UC相关的靶基因数据集。通过整合分析筛选得到LanC治疗UC的共有潜在靶基因集合。对上述靶基因开展基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析。此外，构建蛋白质相互作用（Protein-Protein Interaction, PPI）网络以筛选连接度最高的核心靶基因。后续通过分子对接实验与细胞生物学实验对上述预测结果进行验证。
结果 共鉴定得到23个重叠基因作为LanC治疗UC的潜在靶标，其中KDR、STAT3、ABCB1、CYP3A5及CYP2B6为5个治疗潜力最高的核心靶标。通路富集分析显示，脂肪酸与脂质代谢、外源性物质代谢通路可能是LanC发挥UC治疗作用的关键通路。分子对接模拟结果表明，LanC与上述5个核心靶标均具有良好的结合亲和力。体外实验进一步证实，LanC可显著抑制脂多糖（Lipopolysaccharide, LPS）诱导的RAW264.7细胞促炎细胞因子的表达。
结论 本研究全面阐明了LanC治疗UC的潜在价值及其作用机制，研究结果为优化UC临床治疗方案提供了理论依据，同时凸显了LanC作为UC新型治疗候选药物的应用潜力。