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<p>Henoch-Schönlein purpura nephritis (HSPN) is the most common secondary glomerular disease in children, and is considered a major cause of chronic renal failure. Astragaloside IV (AS-IV) has been shown to protect against HSPN. However, the specific effects and mechanisms of AS-IV in HSPN remain unclear. Using network pharmacology, potential targets of AS-IV were screened via the PharmMapper and SwissTargetPrediction databases, while HSPN related genes were retrieved from OMIM, GeneCards, and DisGeNET databases. Core targets related to AS-IV and HSPN were identified via construction of a protein-protein interaction (PPI) network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed based on these core targets. A compound-target-pathway-disease network was constructed using Cytoscape, incorporating the top 20 pathways associated with HSPN. Molecular docking was then performed to explore the interactions and binding patterns between AS-IV and key target proteins. Subsequently, in vitro experiments using platelet-derived growth factor-BB (PDGF-BB) stimulated human mesangial cells (HMCs) confirmed the findings of the bioinformatics analysis. Through network pharmacological analysis, 75 AS-IV targets intersecting with HSPN were identified. Key targets included EGFR, STAT1, MAPK1, AKT1 and SRC. KEGG enrichment revealed that the Pathways in cancer, PI3K-Akt signaling pathway, and MAPK signaling pathway might play important roles in AS-IV against HSPN. Molecular docking results suggested strong binding affinity between AS-IV and these potential targets. Experimental verification demonstrated that AS-IV (50 and 100 µM) exerted a protective effect against the proliferation of HMCs induced by PDGF-BB. Specifically, AS-IV significantly upregulated the protein expression of p21/p53, and reduced both YAP1 protein levels and Ki67 nuclear staining. Collectively, our findings demonstrate the key targets, primary signaling pathways, and underlying molecular mechanisms of AS-IV in HSPN treatment. These results provide a scientific basis for understanding the complex mechanisms of AS-IV action against HSPN in vitro and suggest its potential, warranting further investigation, as a therapeutic candidate for HSPN.</p>

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Network Pharmacology and Experimental Evidence Identify the Mechanism of Astragaloside IV against Henoch-Schönlein Purpura Nephritis

  • 期刊论文

  • 发表日期：

    2025年6月16日

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  • Shuang Pang,
  • Qinghao Yan,
  • Haiou Xia,
  • Shaowei Liu,
  • Feifei Gu,
  • Yan Xu,
  • Min Li,
  • Liping Yue

摘要

Henoch-Schönlein purpura nephritis (HSPN) is the most common secondary glomerular disease in children, and is considered a major cause of chronic renal failure. Astragaloside IV (AS-IV) has been shown to protect against HSPN. However, the specific effects and mechanisms of AS-IV in HSPN remain unclear. Using network pharmacology, potential targets of AS-IV were screened via the PharmMapper and SwissTargetPrediction databases, while HSPN related genes were retrieved from OMIM, GeneCards, and DisGeNET databases. Core targets related to AS-IV and HSPN were identified via construction of a protein-protein interaction (PPI) network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed based on these core targets. A compound-target-pathway-disease network was constructed using Cytoscape, incorporating the top 20 pathways associated with HSPN. Molecular docking was then performed to explore the interactions and binding patterns between AS-IV and key target proteins. Subsequently, in vitro experiments using platelet-derived growth factor-BB (PDGF-BB) stimulated human mesangial cells (HMCs) confirmed the findings of the bioinformatics analysis. Through network pharmacological analysis, 75 AS-IV targets intersecting with HSPN were identified. Key targets included EGFR, STAT1, MAPK1, AKT1 and SRC. KEGG enrichment revealed that the Pathways in cancer, PI3K-Akt signaling pathway, and MAPK signaling pathway might play important roles in AS-IV against HSPN. Molecular docking results suggested strong binding affinity between AS-IV and these potential targets. Experimental verification demonstrated that AS-IV (50 and 100 µM) exerted a protective effect against the proliferation of HMCs induced by PDGF-BB. Specifically, AS-IV significantly upregulated the protein expression of p21/p53, and reduced both YAP1 protein levels and Ki67 nuclear staining. Collectively, our findings demonstrate the key targets, primary signaling pathways, and underlying molecular mechanisms of AS-IV in HSPN treatment. These results provide a scientific basis for understanding the complex mechanisms of AS-IV action against HSPN in vitro and suggest its potential, warranting further investigation, as a therapeutic candidate for HSPN.