Proanthocyanidins are phenolic compounds abundant in the diet, commonly found in grapes and derivatives, foods known for their health-promoting benefits. There is previous evidence showing the antidiabetic activity of proanthocyanidins, however, their mechanisms of action have not been fully elucidated. This study evaluated the capacity of grape seed proanthocyanidins extract (GSPE) to modulate oxidative stress, nitric oxide levels, mitochondrial dysfunction, apoptosis, and sirtuin expression in endothelial cells EA.hy926 under high glucose condition. In addition, the possible toxic effects of GSPE was evaluated in a zebrafish embryos model. The results showed that GSPE was able to enhance cell viability and avoid the disturbance in redox metabolism induced by high glucose. Moreover, GSPE was able to avoid mitochondria dysfunction and the increased in p53 and poly-(ADP-ribose) polymerase expression induced by high glucose exposition. These effects were attributed to the increase in expression of sirtuin 3, a protein able to regulate mitochondrial function. GSPE in an effective concentration did not show toxic effects in zebrafish embryos model. Taken together, these data elucidate the key molecular target of GSPE for future pharmacological interventions in diabetic patients.

中文翻译：

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葡萄籽原花青素通过增加高糖条件下EA.hy926细胞中sirtuin 3的表达来改善线粒体功能并降低氧化应激。

原花青素是饮食中富含的酚类化合物，通常存在于葡萄及其衍生物中，这些食物以促进健康为名。以前的证据表明原花色素的抗糖尿病活性，但是，其作用机理尚未完全阐明。这项研究评估了葡萄籽原花青素提取物（GSPE）在高葡萄糖条件下调节内皮细胞EA.hy926中氧化应激，一氧化氮水平，线粒体功能障碍，细胞凋亡和瑟土因蛋白表达的能力。此外，在斑马鱼胚胎模型中评估了GSPE可能的毒性作用。结果表明，GSPE能够增强细胞活力并避免高糖诱导的氧化还原代谢紊乱。此外，GSPE能够避免线粒体功能障碍以及高葡萄糖暴露诱导的p53和聚（ADP-核糖）聚合酶表达的增加。这些作用归因于Sirtuin 3的表达增加，Sirtuin 3是一种能够调节线粒体功能的蛋白质。有效浓度的GSPE在斑马鱼胚胎模型中未显示毒性作用。综上所述，这些数据阐明了GSPE在糖尿病患者中未来药理干预中的关键分子靶点。