Therapeutic potential of flavonoids in the treatment of chronic venous insufficiency

Chronic venous insufficiency (CVI) is a common disorder associated with a variety of symptoms in later disease stages; despite the high prevalence of this pathology, suitable pharmaceutical therapies have not been explored to date. In this context, it was recently reported that a chronic increase in venous wall stress or biomechanical stretch is sufficient to cause development of varicose veins. Recent evidence demonstrate that flavonoids are natural substances that convey the circulatory system functionality, playing a key role in blood flow. Particularly, troxerutin, diosmin and horse chestnut extract, appear protective for the management of vascular diseases. The aim of the present study was to evaluate the effect of a flavonoid compound, containing troxerutin, diosmin and horse chestnut extract on in vitro model on HUVECs cells, due to its production of vasculoregulatory and vasculotropic molecules, on an ex-vivo model on mesenteric vessel contraction, to regularize mesenteric microcirculation and on in vivo model of CVI-induced by saphene vein ligation. Furthermore, the flavonoid compound capacity of extensibility and compatibility with peripheral veins was investigated through a tissue block culture study. The degree of absorption, the contractile venous activity, the histological analysis, the immunoistochemical and immunofluorescence evaluation for VEGF and CD34 were performed, together with inflammatory mediators dosage. For the first time, this research revealed the therapeutic potential of a compound, enriched with flavonoids, to be a supportive treatment, suitable to reduce varicose vein pathophysiology and to regularize venous tone.