Ephedrine Attenuates LPS-Induced Acute Lung Injury in Mice by Inhibiting OTUB1 and Promoting K48 Ubiquitination of HIF1α

Acute lung injury (ALI) is a severe inflammatory lung disorder that requires effective therapeutic strategies. Ephedrine (EPH) is the main active component found in medicinal plants of the Ephedra genus and is commonly used to modulate inflammatory responses in various diseases. Hypoxia-inducible factor 1-alpha (HIF1α) is a subunit of hypoxia-inducible factor 1 (HIF1), which plays a critical regulatory role in cellular responses under hypoxic conditions. Moreover, the degradation pathway of HIF1α is regulated by the deubiquitinase Ovarian Tumour Domain-containing Ubiquitin Aldehyde Binding Protein 1 (OTUB1). The aim of this study is to investigate the therapeutic effects of EPH on ALI and its potential therapeutic mechanism. We utilised a lipopolysaccharide (LPS)-induced ALI mouse model and employed various methods for evaluation. Ultimately, our research findings demonstrate that EPH exhibits anti-ALI effects, with the involvement of HIF1α and OTUB1 in the pharmacological actions of EPH. In conclusion, our study results demonstrate that EPH exhibits anti-ALI effects and exerts its protective effects through modulation of the OTUB1 and HIF1α pathways. Our research findings not only lay the foundation for expanding the medicinal applications of EPH but also provide direction for seeking improved treatment strategies for ALI.