Departments Molecular and Cellular Sports Medicine German Sport University Cologne Institute of Cardiovascular Research and Sports Medicine Am Sportpark Müngersdorf 6 Cologne Germany.
Pharmacol Res Perspect. 2016 Feb 8;4(1):e00213. doi: 10.1002/prp2.213. eCollection 2016 Feb.
The red-vine-leaf extract AS195 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 AS195 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 AS195 increases NO bioavailability by decreasing the content of reactive oxygen species (ROS) and increasing antioxidant capacity. Cultured HUVECs and RBCs from healthy volunteers were incubated with AS195 (100 μmol/L), tert-butylhydroperoxide (TBHP, 1 mmol/L) to induce oxidative stress and with both AS195 and TBHP. Endothelial and red blood cell-nitric oxide synthase (RBC-NOS) activation significantly increased after AS195 incubation. Nitrite concentration, a marker for NO production, increased in HUVEC but decreased in RBC after AS195 application possibly due to nitrite scavenging potential of flavonoids. S-nitrosylation of RBC cytoskeletal spectrins and RBC deformability were increased after AS195 incubation. TBHP-induced ROS were decreased by AS195, and antioxidative capacity was significantly increased in AS195-treated cells. TBHP also reduced RBC deformability, but reduction was attenuated by parallel incubation with AS195. Adhesion of HUVEC was also reduced after AS195 treatment. Red-vine-leaf extract AS195 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.
红葡萄叶提取物 AS195 可改善慢性静脉功能不全患者的皮肤供氧和微循环。血流调节与一氧化氮合酶（NOS）依赖性 NO（一氧化氮）产生有关，内皮细胞和红细胞（RBC）已被证明具有各自的 NOS 同工型。研究假设 AS195 可正向影响人脐静脉内皮细胞（HUVEC）和 RBC 中的 NOS 激活。由于微血管疾病患者的氧化应激增加，限制了 NO 的生物利用度，因此进一步假设 AS195 通过降低活性氧（ROS）含量和增加抗氧化能力来增加 NO 的生物利用度。用 AS195（100 μmol/L）孵育来自健康志愿者的培养的 HUVEC 和 RBC、叔丁基过氧化物（TBHP，1 mmol/L）以诱导氧化应激以及同时用 AS195 和 TBHP 孵育。NOS 激活后，内皮细胞和 RBC 的 NO 生成显著增加。NO 产生的标志物亚硝酸盐浓度在 HUVEC 中增加，但在用 AS195 处理后 RBC 中降低，这可能是由于类黄酮的亚硝酸盐清除潜力。AS195 孵育后 RBC 细胞骨架 spectrins 的 S-亚硝基化和 RBC 变形性增加。AS195 降低了 TBHP 诱导的 ROS，并且在用 AS195 处理的细胞中抗氧化能力显著增加。TBHP 还降低了 RBC 的变形性，但通过与 AS195 平行孵育，降低作用减弱。AS195 处理后 HUVEC 的黏附力也降低。红葡萄叶提取物 AS195 可增加 NOS 激活并降低氧化应激。这两种机制均可增加 NO 的生物利用度，改善细胞功能，从而可能解释其在健康和疾病状态下对微循环的改善作用。
