The red-vine-leaf extract increases nitric oxide synthase–dependent nitric oxide generation and decreases oxidative stress in endothelial and red blood cells

ByMarijke Graua, Birgit B€olcka, Daniel Alexander Bizjak, Christina Julia Annika Stabenow &Wilhelm Bloch

Source: Pharma Res Per, 4(1), 2016, e00213,

The red-vine-leaf extract improves cutaneous oxygen supply and the microcirculation in patients suffering from chronic venous insufficiency. Regulation of blood flow was associated to nitric oxide synthase (NOS)-dependent NO (nitric oxide) production, and endothelial and red blood cells(RBC) have been shown to possess respective NOS isoforms. It was hypothesized that RED-VINE-LEAF EXTRACT positively affects NOS activation in human umbilical vein endothelial cells (HUVECs) and RBC. Because patients with microvascular disorders show increased oxidative stress which limits NO bioavailability, it was further hypothesized that RED-VINE-LEAF EXTRACT increases NO bioavailability by decreasing the content of reactive oxygen species (ROS) and increasing antioxidantcapacity. Cultured HUVECs and RBCs from healthy volunteers were incubated with RED-VINE-LEAF EXTRACT (100 lmol/L), tert-butylhydroperoxide (TBHP, 1 mmol/L) toinduce oxidative stress and with both RED-VINE-LEAF EXTRACT and TBHP. Endothelial and red blood cell–nitric oxide synthase (RBC-NOS) activation significantly increasedafter RED-VINE-LEAF EXTRACT incubation. Nitrite concentration, a marker for NO production, increased in HUVEC but decreased in RBC after RED-VINE-LEAF EXTRACT application possiblydue to nitrite scavenging potential of flavonoids. S-nitrosylation of RBC cytoskeletal spectrins and RBC deformability were increased after RED-VINE-LEAF EXTRACT incubation. TBHP-induced ROS were decreased by RED-VINE-LEAF EXTRACT, and antioxidative capacity was significantly increased in RED-VINE-LEAF EXTRACT-treated cells. TBHP also reduced RBC deformability, but reduction was attenuated by parallel incubation with RED-VINE-LEAF EXTRACT. Adhesion of HUVEC was also reduced after RED-VINE-LEAF EXTRACT treatment. Red vine-leaf extract RED-VINE-LEAF EXTRACT increases NOS activation and decreases oxidative stress. Both mechanisms increase NO bioavailability, improve cell function, and may thus account for enhanced microcirculation in both health and disease.