Baicalin Targeting ALOX15 Inhibits Ferroptosis of Lung Epithelial Cells and Alleviates Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by chronic inflammation and irreversible airflow limitation. Ferroptosis has been implicated in the pathogenesis of COPD. In this study, we investigated the potential of baicalin, a natural compound with anti-inflammatory properties, to target ALOX15 and inhibit ferroptosis in lung epithelial cells, thereby alleviating COPD. Overexpression ALOX15 of BEAS-2B cells was induced by RSL-3, an activator of ferroptosis, to mimic the inflammatory environment in COPD. The effects of baicalin on ferroptosis were assessed by measuring cell viability, lipid peroxidation, lipid ROS, and ferrous ion (Fe2+). The expression of OH-1, ALOX15, and GPX4 was evaluated using Western blotting. Baicalin treatment significantly increased cell viability in RSL-3 induced epithelial cells. Our findings also demonstrate that baicalin significantly increases cell viability and reduces lipid ROS and Fe2+ levels, thereby inhibiting ferroptosis and improving cell viability, irrespective of ALOX15 expression Furthermore, baicalin upregulated the expression of GPX4, a key regulator of ferroptosis. Importantly, baicalin treatment inhibited ALOX15 expression, a critical enzyme involved in lipid peroxidation. Our study demonstrates that baicalin targeting ALOX15 inhibits ferroptosis of lung epithelial cells and alleviates COPD. These findings provide a basis for further research and development of baicalin-based therapies for COPD patients, with the potential to improve their clinical outcomes and quality of life.