Diosmin Attenuates Age-Associated Vascular Oxidative Stress and Endothelial Dysfunction in Aged Rats

Vascular aging is driven by a self-sustaining interplay between oxidative stress and chronic low-grade inflammation, collectively referred to as inflammaging. Diosmin, a citrus-derived flavonoid with antioxidant and anti-inflammatory properties, has not previously been investigated in this context. Young (10-week-old) and aged (40-week-old) male Sprague-Dawley rats received diosmin (50 mg/kg/day) or vehicle for 3 months. Vascular function was assessed in mesenteric resistance arteries using pressure myography, while oxidative stress was evaluated by dihydroethidium and mitoSOX staining. Circulating malondialdehyde (MDA), tumor necrosis factor (TNF), lipopolysaccharide-binding protein (LBP) vascular expression of Nos3, Gpx1, Sod2 and Xdh were measured. Aging was associated with impaired endothelium-dependent vasorelaxation, increased vascular DHE and MitoSOX fluorescence and elevated circulating MDA and LBP levels. Chronic diosmin supplementation partially restored endothelial function. The improvement in endothelial function was consistent with a partial preservation of NO-dependent endothelial function, although NO production and bioavailability were not measured directly. Diosmin also significantly reduced vascular DHE and MitoSOX fluorescence in aged animals. These effects were accompanied by decreased plasma MDA and LBP levels, whereas TNF remained unchanged. Diosmin did not significantly affect Nos3, Gpx1 or Sod2 gene's expression, but it attenuated the age-related upregulation of Xdh. Overall, diosmin attenuated age-associated vascular oxidative stress and partially improved endothelial function in aged rats. Although the reduction in circulating LBP suggests a possible effect on selected systemic signals associated with endotoxin exposure, additional inflammatory markers and mechanistic studies will be required to determine whether diosmin modulates vascular inflammaging.