Laboratory of Microbiology and Probiotics, Institute of Nutrition and Food Technology, University of Chile, Av. Macul 5540, Santiago, P.O. Box 138-11, Chile.
Chem Biol Interact. 2012 Feb 5;195(3):199-205. doi: 10.1016/j.cbi.2011.12.007. Epub 2011 Dec 27.
The beneficial effects of dietary polyphenols on health are due not only to their antioxidant properties but also to their antibacterial, anti-inflammatory and/or anti-tumoral activities. It has recently been proposed that protection of mitochondrial function (which is altered in several diseases such as Alzheimer, Parkinson, obesity and diabetes) by these compounds, may be important in explaining the beneficial effects of polyphenols on health. The aim of this study was to evaluate the protective effects of dietary polyphenols quercetin, rutin, resveratrol and epigallocatechin gallate against the alterations of mitochondrial function induced by indomethacin (INDO) in intestinal epithelial Caco-2 cells, and to address the mechanism involved in such damaging effect by INDO, which generates oxidative stress. INDO concentration dependently decreases cellular ATP levels and mitochondrial membrane potential in Caco-2 cells after 20min of incubation. INDO also inhibits the activity of mitochondrial complex I and causes accumulation of NADH; leading to overproduction of mitochondrial O(2)()(-), since it is prevented by pyruvate. Quercetin (0.01mg/ml), resveratrol (0.1mg/ml) and rutin (1mg/ml) protected Caco-2 cells against INDO-induced mitochondrial dysfunction, while no protection was observed with epigallocatechin gallate. Quercetin was the most efficient in protecting against mitochondrial dysfunction; this could be due to its ability to enter cells and accumulate in mitochondria. Additionally its structural similarity with rotenone could favor its binding to the ubiquinone site of complex I, protecting it from inhibitors such as INDO or rotenone. These findings suggest a possible new protective role for dietary polyphenols for mitochondria, complementary of their antioxidant property. This new role might expand the preventive and/or therapeutic use of PPs in conditions involving mitochondrial dysfunction and associated with increased oxidative stress at the cellular or tissue levels.
膳食多酚对健康的有益影响不仅归因于其抗氧化特性，还归因于其抗菌、抗炎和/或抗肿瘤活性。最近有人提出，这些化合物对线粒体功能的保护（在阿尔茨海默病、帕金森病、肥胖症和糖尿病等几种疾病中会发生改变）可能对解释多酚对健康的有益影响很重要。本研究旨在评估膳食多酚槲皮素、芦丁、白藜芦醇和表没食子儿茶素没食子酸酯对吲哚美辛（INDO）诱导的肠上皮 Caco-2 细胞线粒体功能改变的保护作用，并探讨 INDO 产生氧化应激时产生这种损伤作用的机制。INDO 浓度依赖性地降低孵育 20min 后 Caco-2 细胞中的细胞 ATP 水平和线粒体膜电位。INDO 还抑制线粒体复合物 I 的活性并导致 NADH 积累；导致线粒体 O(2)()(-)的过度产生，因为它被丙酮酸所阻止。槲皮素（0.01mg/ml）、白藜芦醇（0.1mg/ml）和芦丁（1mg/ml）可保护 Caco-2 细胞免受 INDO 诱导的线粒体功能障碍，而表没食子儿茶素没食子酸酯则没有保护作用。槲皮素在保护线粒体功能障碍方面最为有效；这可能是由于其进入细胞并在线粒体中积累的能力。此外，其与鱼藤酮的结构相似可能有利于其与复合物 I 的泛醌结合位点结合，从而保护其免受 INDO 或鱼藤酮等抑制剂的影响。这些发现表明膳食多酚可能对线粒体具有新的保护作用，补充了其抗氧化特性。这种新作用可能会扩大 PPs 在涉及线粒体功能障碍和与细胞或组织水平增加氧化应激相关的情况下的预防和/或治疗用途。
