Scholarlink

<p>This study aimed to identify and validate key target genes of <i>Astragalus membranaceus</i> and <i>Ephedra</i> in pediatric obesity-associated asthma using integrated bioinformatics and network pharmacology approaches, with the goal of informing potential therapeutic strategies. Gene expression datasets related to pediatric obesity (GSE205668, GSE104815) and asthma (GSE147878, GSE143303) were analyzed. Candidate genes were obtained by overlapping differentially expressed genes with known targets of <i>Astragalus membranaceus</i> and <i>Ephedra</i>. Machine learning algorithms and expression analyses were applied to refine the list of key genes. Two nomogram prediction models were constructed based on these genes and assessed for diagnostic efficacy. Subsequent analyses included functional enrichment, immune cell infiltration profiling, molecular docking, and validation through reverse transcription quantitative PCR (RT-qPCR). The genes <i>AKR1C3</i> and <i>KYNU</i> were identified as key targets associated with both pediatric obesity and asthma. RT-qPCR results demonstrated significantly elevated expression of <i>AKR1C3</i> and <i>KYNU</i> in samples from individuals with obesity-related asthma (<i>P</i> &lt; 0.01). The developed nomogram models accurately predicted disease risk. Functional enrichment analysis indicated that these genes were co-enriched in pathways including allograft rejection in the context of obesity and primary immunodeficiency in the context of asthma. Immune cell profiling indicated alterations in 18 immune cell types in pediatric obesity and 5 in asthma. Molecular docking results indicated that kaempferol and apigenin exhibited strong binding affinities with <i>AKR1C3</i>, while canavanine effectively targeted <i>KYNU</i>, with a binding energy of − 9.5&#xa0;kcal/mol between <i>AKR1C3</i> and kaempferol. <i>AKR1C3</i> and <i>KYNU</i> were identified and experimentally validated as potential therapeutic targets in pediatric asthma associated with obesity. These findings support the therapeutic relevance of <i>A. membranaceus</i> and <i>Ephedra</i>-derived compounds in modulating key molecular pathways implicated in this comorbid condition.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Network pharmacology identifies AKR1C3 and KYNU as potential targets of Astragalus Membranaceus and Ephedra in pediatric obesity-associated asthma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月9日

查看全文
  • Jie-lin Chen,
  • Xiao-juan Liu,
  • Hai-yan Zhao,
  • Gai-hong Zhao,
  • Ming-dong Gao

摘要

This study aimed to identify and validate key target genes of Astragalus membranaceus and Ephedra in pediatric obesity-associated asthma using integrated bioinformatics and network pharmacology approaches, with the goal of informing potential therapeutic strategies. Gene expression datasets related to pediatric obesity (GSE205668, GSE104815) and asthma (GSE147878, GSE143303) were analyzed. Candidate genes were obtained by overlapping differentially expressed genes with known targets of Astragalus membranaceus and Ephedra. Machine learning algorithms and expression analyses were applied to refine the list of key genes. Two nomogram prediction models were constructed based on these genes and assessed for diagnostic efficacy. Subsequent analyses included functional enrichment, immune cell infiltration profiling, molecular docking, and validation through reverse transcription quantitative PCR (RT-qPCR). The genes AKR1C3 and KYNU were identified as key targets associated with both pediatric obesity and asthma. RT-qPCR results demonstrated significantly elevated expression of AKR1C3 and KYNU in samples from individuals with obesity-related asthma (P < 0.01). The developed nomogram models accurately predicted disease risk. Functional enrichment analysis indicated that these genes were co-enriched in pathways including allograft rejection in the context of obesity and primary immunodeficiency in the context of asthma. Immune cell profiling indicated alterations in 18 immune cell types in pediatric obesity and 5 in asthma. Molecular docking results indicated that kaempferol and apigenin exhibited strong binding affinities with AKR1C3, while canavanine effectively targeted KYNU, with a binding energy of − 9.5 kcal/mol between AKR1C3 and kaempferol. AKR1C3 and KYNU were identified and experimentally validated as potential therapeutic targets in pediatric asthma associated with obesity. These findings support the therapeutic relevance of A. membranaceus and Ephedra-derived compounds in modulating key molecular pathways implicated in this comorbid condition.