Effects of Vitis vinifera leaf extracts on inflammation and vascular permeability

Wine production leads to large amounts of by-products, such as leaves, which are rich in flavonoids that are effective in venous insufficiency [1], [2]. Venous insufficiency results from venous hypertension and leads to edema, skin lesions and eventually venous ulceration. It is characterized by increased vascular leakage, inflammation factors (IL-6, TGF-1), adhesion molecules (sICAM, sVCAM) and metalloproteases (MMP2, MMP9). Here, we investigated the effect of Vitis vinifera leaf extracts on inflammation and vascular permeability. Human endothelial (EA. hy926) and fibroblast (DLF) cell lines were pretreated with six leaf extracts (1 µg/ml). Inflammation was induced by TNA-α (100 ng/ml). Twenty-four hours following TNF-α stimulation, the levels of secreted IL-6, TGF-β1, sVCAM, sICAM and MMP9 levels were quantified with ELISA. The two most effective extracts were tested in the carrageenan (2% w/v)-induced paw edema model and the VEGF (50 ng)-induced vascular leakage model in mice, using the EVANS blue method. The aqueous extract E13 and the enriched phenolic fraction E15 were the most effective in reducing TNF-α induced IL-6, TGF-β1, sICAM, sVCAM and MMP9 in both EA. hy925 and DLF cells. Also, E13 (30 mg/Kg) and E15 (30 mg/Kg) reduced carrageenan-induced edema and E13 (30 mg/Kg and 100 mg/Kg) significantly reduced vascular leakage induced by VEGF. In summary, the aqueous extract E13, effectively reduced inflammation and vascular leakage in vitro and in vivo suggesting it could be further evaluated in humans suffering from venous insufficiency.