Shikonin alleviates high-fat diet-induced vascular aging and dysfunction by inhibiting oxidative stress and mitochondrial damage.

backgroundVascular aging and dysfunction are key contributors to the development of atherosclerosis, particularly under metabolic stress conditions such as high-fat diet (HFD). This study aimed to investigate the protective effect of the natural naphthoquinone compound shikonin (SKN) against HFD-induced vascular injury and to elucidate the underlying mechanisms. METHODS AND

resultsMale Sprague Dawley rats were fed a HFD for 10 consecutive weeks to induce metabolism-related vascular injury. From the fourth week onward, SKN was administered via intraperitoneal injection for 7 weeks. Endothelium-dependent vasodilation was assessed by acetylcholine-induced vascular reactivity. Histological changes in the aorta were examined using H&E, Masson’s trichrome, and Oil Red O staining. Oxidative stress markers, including ROS, MDA, GSH, SOD, and NADPH, were measured. Protein expression levels of NOX2, NOX4, P-p53, p21, DRP1, and FIS1 were detected by immunofluorescence and Western blotting. SKN significantly improved endothelial function and reduced collagen deposition and lipid accumulation in the aorta of HFD-fed rats. It also decreased NOX2/NOX4 expression, reduced MDA levels, and elevated GSH, SOD, and NADPH, indicating restored redox balance. Additionally, SKN downregulated vascular senescence markers (P-p53, p21) and mitochondrial fission proteins (DRP1, FIS1), suggesting attenuation of mitochondrial dysfunction and vascular aging.

conclusionSKN alleviates HFD-induced vascular dysfunction and senescence by suppressing NOX-mediated oxidative stress and modulating mitochondrial dynamics, highlighting its therapeutic potential in metabolic vascular diseases.