Aloperine alleviates lung ischemia-reperfusion injury by modulating ferroptosis via the STAT-1 pathway.

Abstract

Lung ischemia-reperfusion injury (LIRI) is a severe complication of lung transplantation and acute respiratory distress syndrome, leading to significant pulmonary dysfunction. Aloperine, a natural alkaloid derived from Sophora alopecuroides, has demonstrated promising pharmacological effects on various ischemia-reperfusion injuries. However, its role in LIRI remains underexplored. Our experimental results revealed that aloperine significantly alleviated bilateral lung tissue damage induced by ipsilateral ischemia-reperfusion, with a mechanism closely linked to the regulation of inflammatory responses and apoptosis-related proteins. Further studies demonstrated that aloperine specifically activated the STAT-1 signaling pathway, as evidenced by markedly increased STAT-1 phosphorylation levels in lung tissue damage in the ipsilateral (ischemic) and contralateral (non-ischemic) lung, thereby inhibiting ferroptosis. Notably, the STAT-1 inhibitor AG490 completely reversed the lung-protective effects of aloperine, confirming the protective effects of STAT-1. These findings provide critical experimental evidence for the potential clinical application of aloperine in LIRI intervention.