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

Year: 2025

Type: article

Abstract: 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.

Source: Fitoterapia

DOI: 10.1016/j.fitote.2025.106829

Authors: Jong Min Kim, Hyun-Jin Na, Yiseul Kim, Sang Hee Lee, Chang Hwa Jung, Mi Jeong Sung

Institution: Korea Food Research Institute

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,950