Rhizoma Dioscoreae Nipponicae relieves asthma through inducing the ferroptosis of eosinophils and inhibiting the p38 MAPK signaling pathway

Objectives: Rhizoma Dioscoreae Nipponicae (RDN) is a traditional Chinese medicine that widely applied in the treatment of human diseases. This study aims to explore the therapeutic potential of RDN in asthma and the underlying mechanisms. Methods: A mouse model of asthma was established by the stimulation of ovalbumin (OVA). HE staining was performed to detect the pathological injuries of tracheal tissues. The protein expression of collagen Ⅰ, FN1, α-SMA (airway remodeling markers), and p-p38 (a marker of the p38 MAPK pathway) were detected by Western blot. Eosinophils were then isolated from the model mice. Cell viability and ROS level were measured by CCK-8 and Flow cytometry, respectively. The mRNA expression of GPX4 and ACSL4 (ferroptosis markers) in eosinophils were measured by qRT-PCR. Results: RDN significantly reduced the numbers of total cells and eosnophils in BALF, inhibited inflammatory cell infiltration, and down-regulated remodeling markers (Collagen Ⅰ, FN1, and α-SMA) in OVA-induced mice. The p38 MAPK pathway was blocked by the intervention of RDN in the model mice, and its blocking weakens the poor manifestations of OVA-induced asthma. In addition, RDN induced the ferroptosis of eosnophils both in vitro and in vivo. Blocking of the p38 MAPK pathway also enhanced the ferroptosis of eosnophils in vitro, evidenced by the decreased cell viability and GPX4 expression, and increased ROS level and ACSL4 expression. Conclusion: RDN induced the ferroptosis of eosinophils through inhibiting the p38 MAPK pathway, contributing to the remission of asthma.