Ex Vivo Study of the Vasomotor and Anti-Inflammatory Activity of Class 2 Elastic Venous Compression Devices Combined with Diosmetin-3-O-β-D-Glucuronide

Diosmin, a flavonoid, is widely used to alleviate the symptoms of chronic venous disease (CVD), while compression stockings remain a key component of its conservative management. This study used an ex vivo model of human skin explants to evaluate the vasomotor and anti-inflammatory effects of a class II elastic venous compression model (EVC2), applied alone or in combination with diosmetin-3-O-β-D-glucuronide (DT), the major circulating metabolite of diosmin. The explants were exposed to substance P to induce neurogenic inflammation, after which they were treated with EVC2, DT at a concentration of 2700 pg/mL, or both. Compared with substance P alone, all treatments led to a significant reduction in capillary dilation and IL-8 secretion, as well as a change in endothelial CD34 expression. While the combination improved all parameters, only significant additional effects were observed for reducing low CD34 expression versus DT alone (77% for score 0, no CD34 expression, p = 0.043; 62.1% for score 1, low CD34 expression, p = 0.013), and for decreasing IL-8 versus EVC2 alone (41.2%, p = 0.033). These findings suggest vasomotor and anti-inflammatory effects of DT and mechanical compression, and highlight their combined effects on inflammatory parameters in CVD.