• Combined xanthohumol and swimming significantly improved liver injury in MAFLD rats compared to either intervention alone.
• The combination therapy enhanced Nrf2-mediated ferroptosis defense, upregulating GPX4 and related genes while reducing iron overload and lipid peroxidation.
• Swimming was chosen for its unique non-weight-bearing, whole-body metabolic stimulation, distinct from land-based exercise.
• The study suggests a promising combined therapeutic strategy for MAFLD targeting ferroptosis.