Magnolia kobus DC. suppresses neointimal hyperplasia by regulating ferroptosis and VSMC phenotypic switching in a carotid artery ligation mouse model

Background: Magnolia kobus DC (MO), as a plant medicine, has been reported to have various physiological activities, including neuroprotective, anti-inflammatory, and anti-diabetic effects. However, vascular protective effects of MO remain incompletely understood. In this study, we evaluated the vascular protective effect of MO against ferroptosis in a carotid artery ligation (CAL)-induced neointimal hyperplasia mouse model and in aortic thoracic smooth muscle A7r5 cells.

Methods: This study was conducted to estimate the vascular protective effects of MO by systematically measuring histopathological analysis and western blot analysis in CAL animal model. In vitro protective effects of MO were evaluated by estimating cell viability, reactive oxygen species (ROS) content, glutathione (GSH) levels, lipid peroxidation, mitochondrial morphological change, cell proliferation, migration, western blot analysis, and qRT-PCR against erastin (Era)-induced A7r5 cells.

Results: MO intake significantly improved neointimal formation, inhibited ferroptosis and vascular smooth muscle cell (VSMC) phenotypes, and ameliorated the antioxidant system of carotid artery tissues. In addition, MO treatment effectively ameliorated Era-induced ferroptotic cytotoxicity, including cellular death, ROS production, and cell migration status. MO treatment also suppressed proliferation and migration in Era-induced A7r5 cells. MO considerably regulated Era-induced abnormal mechanisms related to ferroptotic changes, VSMC phenotype switching, and the ROS scavenging system in A7r5 cells.

Conclusion: MO has the potential for use as a functional food supplement, nutraceutical, or medicinal food, with protective effects on vascular health by regulating ferroptosis and VSMC phenotypic switching.