Rhizoma Dioscoreae Nipponicae attenuates airway remodeling and angiogenesis-related changes in asthma with altered mTOR/4EBP1/HIF-1α/VEGF pathway markers

<h2>Abstract</h2><h3>Background</h3> Asthma is a chronic inflammatory airway disease characterized by airway remodeling and hyperresponsiveness. Angiogenesis is a key contributor to airway remodeling and disease progression. Rhizoma Dioscoreae Nipponicae (RDN), a traditional Chinese medicine, has shown anti-inflammatory and anti-angiogenic potential, but its effects on asthma-associated airway remodeling remain unclear. <h3>Methods</h3> The chemical profile of the RDN extract was characterized using UHPLC-Q Exactive Orbitrap MS/MS. An ovalbumen-induced mouse model of asthma and C166 mouse endothelial cells were used to examine the effects of RDN treatment. Histopathological changes were assessed using H&E and Masson's trichrome staining. mRNA and protein expression levels of key components in the mTOR/4EBP1/HIF-1α/VEGF signaling pathway were analyzed by qPCR and Western blot. <h3>Results</h3> UHPLC-Q Exactive Orbitrap MS/MS analysis tentatively annotated 2509 constituents and demonstrated good batch-to-batch chemical consistency of the RDN extract. Compared with the model group, RDN treatment significantly reduced the airway inflammation score by approximately 39.5% (<i>P</i> < 0.01), an effect comparable to that of prednisone. It also decreased the collagen area ratio by approximately 62.7% (<i>P</i> < 0.05). RDN also significantly decreased the protein levels of mTOR, 4EBP1, HIF-1α, and VEGF in both lung tissue and C166 cells (<i>P</i> < 0.05). <h3>Conclusion</h3> RDN alleviated airway inflammation and remodeling at the histopathological level, and these effects were associated with downregulation of markers within the mTOR/4EBP1/HIF-1α/VEGF pathway. These findings suggest that RDN may be a promising therapeutic agent for ameliorating airway remodeling in asthma. Future studies incorporating analyses of phosphorylation states are warranted to further clarify the underlying mechanisms.