Integrative network pharmacology and transcriptomics analysis reveals the multi-target anti-allergic mechanism of...

Allergic diseases, characterized by an excessive immune response to allergens, pose a significant global health challenge with limited curative options. Ginsenoside Rh1, a rare ginsenoside derived from ginseng, has shown potential in alleviating allergic inflammation, yet its comprehensive mechanism remains unclear. This study employed an integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and transcriptomics analysis to systematically explore the multi-target mechanisms of Rh1 against allergy. A total of 272 potential targets of Rh1 related to allergic reactions were identified. Subsequent protein-protein interaction (PPI) network analysis and molecular docking identified four key targets: ALB, CASP3, NFKB1 and STAT3. Molecular dynamics simulations indicated stable binding interactions between Rh1 and these targets. Functional enrichment analysis revealed that the therapeutic effects were primarily associated with the MAPK signaling pathway, Th17 cell differentiation pathway and PI3K-Akt signaling pathway. To contextualize these predictions within human disease biology, we analyzed public transcriptomic datasets (GSE50223, GSE232127) from allergic patients. This independent analysis showed that the predicted core targets are dysregulated in human allergy and that key pathways such as IL-6/JAK/STAT3 signaling are enriched, underscoring their relevance to Th17/IL-17 axis activation. These findings suggest that ginsenoside Rh1 may mitigate allergic reactions through a multi-target and multi-pathway network, providing a theoretical basis for its development as a promising anti-allergic agent.

The online version contains supplementary material available at 10.1007/s40203-026-00705-5.