Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti, 9, 20133 Milanο, Italy.
Indena S.p.A. R&D, Milan, Italy.
Phytomedicine. 2017 Feb 15;25:39-44. doi: 10.1016/j.phymed.2016.12.015. Epub 2016 Dec 23.
Vitis vinifera L. (grape seed extract) is a natural source of proanthocyanidins with antioxidant and free radical-scavenging activities.
Grape seed extract supplementation may prevent vascular endothelium impairment associated with diabetes mellitus in rat pulmonary artery.
We evaluated endothelial function of rat pulmonary artery ex-vivo at the intermediate stage (4 weeks) of streptozotocin (STZ)-induced diabetes mellitus. We also evaluated the protective effect of grape seed extract administered daily, beginning the day after diabetes induction, or 15 days after diabetes induction, until the day of sacrifice. In addition, we compared the effect of grape seed extract supplementation with that of vitamin C.
Rats were made diabetic with streptozotocin (STZ, 65mg/kg i.v.). Thirty days later rats were sacrificed and pulmonary vessels reactivity and endothelial function compared to that of age-matched healthy animals.
Concentration-response curves to ACh, NE, sodium nitroprusside (NO donor), but not to histamine and iloprost (prostacyclin analog), were significantly altered 4 weeks after STZ-injection. Antioxidant supplementation (3mg/kg/day) with either vitamin C or grape seed extract, starting the day after diabetes induction, significantly improved vasodilation to ACh and SNP. Norepinephrine-induced contractions were preserved by grape seed extract, but not vitamin C supplementation. Conversely, vitamin C but not grape seed extract showed beneficial effects contrasting the loss of body weight in diabetic animals. Abnormal vascular function was not reversed when antioxidant supplementations were postponed 15 days after the induction of diabetes.
This study provides scientific support for the therapeutic potential of an antioxidant therapy in endothelial impairment associated with diabetes. A daily supplementation of grape seed proanthocyanidins and/or vitamin C given at the earlier stage of disease may have a complementary role in the pharmacological therapy of diabetes and pulmonary vascular dysfunction.
葡萄(Vitis vinifera L.)籽提取物是一种原花青素的天然来源，具有抗氧化和清除自由基的活性。
葡萄籽提取物的补充可能会预防糖尿病大鼠肺动脉血管内皮损伤。
我们评估了链脲佐菌素(STZ)诱导的糖尿病大鼠中期(4 周)肺动脉的内皮功能。我们还评估了葡萄籽提取物的保护作用，每日给予，从糖尿病诱导后第 1 天开始，或糖尿病诱导后第 15 天开始，直至处死。此外，我们比较了葡萄籽提取物补充与维生素 C 补充的效果。
大鼠用链脲佐菌素(STZ，65mg/kg 静脉注射)制成糖尿病。30 天后，处死大鼠，与年龄匹配的健康动物比较肺血管反应性和内皮功能。
STZ 注射后 4 周，ACh、NE、硝普钠(NO 供体)的浓度-反应曲线显著改变，但组胺和伊洛前列素(前列环素类似物)的曲线没有改变。抗氧化剂补充(每天 3mg/kg)，无论是用维生素 C 还是葡萄籽提取物，从糖尿病诱导后第 1 天开始，都显著改善了对 ACh 和 SNP 的血管舒张作用。葡萄籽提取物可维持去甲肾上腺素诱导的收缩，但维生素 C 补充则不能。相反，维生素 C 但不是葡萄籽提取物补充剂显示出有益的效果，与糖尿病动物体重减轻相反。当抗氧化剂补充在糖尿病诱导后 15 天推迟时，异常的血管功能没有得到逆转。
本研究为抗氧化治疗在糖尿病相关内皮损伤中的治疗潜力提供了科学依据。在疾病的早期阶段，每天补充葡萄籽原花青素和/或维生素 C 可能在糖尿病和肺血管功能障碍的药物治疗中具有互补作用。
