Exploring the Therapeutic Potential of Isorhamnetin in the Treatment of Chronic Obstructive Pulmonary Disease via the Ferroptosis Pathway: A Network Pharmacology and Experimental Study

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic airway disease globally, with ferroptosis playing a role in its occurrence and progression. Isorhamnetin (ISO) has been shown to have anti-inflammatory and antioxidant properties, but its therapeutic effect on COPD and underlying mechanism are not well understood. This study aimed to investigate the therapeutic potential of ISO in COPD using network pharmacology and experimental validation. Through analysis, 11 potential targets for ISO treatment in COPD were identified, with the NRF2/SLC7A11/GPX4pathway playing a key role. Molecular docking studies suggested that ISO may bind to NRF2, SLC7A11, NQO1, AKR1C3, and AKR1C1. Experimental results demonstrated that ISO reduced ferroptosis induced by cigarette smoke extract in BEAS-2B cells and decreased airway inflammation in a mouse COPD model, while upregulating the expression of NRF2, SLC7A11, and GPX4. Overall, these findings provide insights into the potential therapeutic effects of ISO on COPD by targeting ferroptosis in the airway epithelium, with the NRF2/SLC7A11/GPX4pathway being a key mechanism. This study contributes to a better understanding of COPD and airway inflammation, offering potential implications for the development of novel therapeutic strategies.