Wang Xinyu, Yan Changhong, Wang Tong, Li Yajing, Zheng Zeyi
Inner Mongolia Medical University, Hohhot, China.
Baotou Central Hospital, Baotou, China.
Cell Biochem Biophys. 2025 Mar;83(1):403-414. doi: 10.1007/s12013-024-01471-x. Epub 2024 Aug 24.
Luteolin is a naturally occurring flavonoid. The effectiveness of luteolin-rich drugs in treating gastro-esophageal reflux disease (GERD) through traditional Chinese medicine has been demonstrated. This study aimed to identify the potential targets and mechanisms of action of luteolin for the treatment of GERD. An innovative approach combining network pharmacology and molecular dynamics was used to explore the potential therapeutic mechanisms of luteolin and to facilitate the further development of GERD treatment. Drug and disease target information was screened from public databases to obtain 159 intersecting targets through the construction of Venn diagrams. Subsequently, a protein‒protein interaction (PPI) network was constructed, and 10 core targets were identified. Through Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, relevant biological processes, cellular components, and molecular functions related to the treatment of GERD were identified and revealed. KEGG pathway analyses showed enrichment of signaling pathways, including the TNF, IL-17, NF-kappa B, and Toll-like receptor pathways. The molecular docking results indicated that luteolin can effectively bind to 10 core targets. Finally, molecular dynamics simulations confirmed the formation of stable protein‒ligand complexes when IL6 binds to luteolin. In conclusion, network pharmacology, molecular docking, and molecular dynamics simulations were utilized to investigate the mechanism by which luteolin treats GERD. These findings establish a theoretical foundation for future research on the efficacy of luteolin in treating GERD.
木犀草素是一种天然存在的黄酮类化合物。富含木犀草素的药物通过传统中药治疗胃食管反流病（GERD）的有效性已得到证实。本研究旨在确定木犀草素治疗GERD的潜在靶点和作用机制。采用网络药理学和分子动力学相结合的创新方法，探索木犀草素的潜在治疗机制，促进GERD治疗的进一步发展。从公共数据库中筛选药物和疾病靶点信息，通过构建维恩图获得159个交集靶点。随后，构建了蛋白质-蛋白质相互作用（PPI）网络，确定了10个核心靶点。通过基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析，确定并揭示了与GERD治疗相关的生物过程、细胞成分和分子功能。KEGG通路分析显示信号通路富集，包括TNF、IL-17、NF-κB和Toll样受体通路。分子对接结果表明木犀草素能有效结合10个核心靶点。最后，分子动力学模拟证实当IL6与木犀草素结合时形成稳定的蛋白质-配体复合物。总之，利用网络药理学、分子对接和分子动力学模拟研究了木犀草素治疗GERD的机制。这些发现为未来木犀草素治疗GERD疗效的研究奠定了理论基础。
