Justicia procumbens ameliorates aortic aging via ferroptosis regulation in senescent mice and vascular smooth muscle cells

Vascular aging involves structural remodeling, oxidative stress, lipid peroxidation, and phenotypic switching of vascular smooth muscle cells (VSMCs), all contributing to age-related cardiovascular diseases. Ferroptosis, a regulated iron-dependent cell death, is a key mechanism of vascular aging. Justicia procumbens (JP), a medicinal plant rich in lignans and flavonoids, exhibits antioxidant properties; however, its effects on vascular aging are unclear. This study investigated the vascular protective effects of JP using senescent mice and Erastin-induced A7r5 smooth muscle cells. In aged mice, JP suppressed aortic thickening, reduced serum iron levels, and normalized transferrin receptor and apoptosis-inducing factor mitochondria-associated 2 expression. JP attenuated ferroptosis by decreasing the levels of 4-hydroxynonenal, prostaglandin-endoperoxide synthase 2, and acyl-CoA synthetase long-chain family member 1, and restoring the levels of solute carrier family 7 member 11 and glutathione peroxidase 4. Furthermore, JP preserved the expression of the VSMC contractile markers (alpha-smooth muscle actin, smooth muscle 22 alpha, and calponin), reduced the level of the synthetic marker osteopontin, and enhanced the activity of antioxidant enzymes (superoxide dismutase, catalase, and NADPH oxidase 1). In vitro, JP protected A7r5 cells from ferroptosis-induced cytotoxicity, promoted proliferation and migration, and restored ferroptosis and antioxidant markers. These results suggest that JP mitigates vascular aging by modulating ferroptosis, iron homeostasis, oxidative stress, and VSMC phenotype. JP may serve as a promising natural therapeutic agent for preventing age-related vascular degeneration and promoting vascular health.