Antioxidant Properties of Unripe Carica papaya Fruit Extract and Its Protective Effects against Endothelial Oxidative Stress

It has been proven that high consumption of fruit and vegetable lowers the risks of cardiovascular and other oxidative stress-related diseases. Here we evaluated the effects of a tropical fruit, unripe Carica papaya (UCP), on endothelial protection against oxidative damage induced by H(2)O(2). The antioxidant properties of UCP were investigated using the assays of FRAP and ORAC and specific ROS scavenging activities (H(2)O(2), O(2)(•−), OH(•), HOCl). Cytoprotective property was tested in human endothelial cell line EA.hy926 with respect to cell survival, intracellular ROS levels, antioxidant enzyme activities (CAT, SOD, GPX), survival/stress signaling (AKT, JNK, p38), and nuclear signaling (Nrf2, NF-kB). UCP processed high antioxidant activity and scavenging activity against H(2)O(2)> OH(•)> O(2)(•−)> HOCl, respectively. UCP improved cell survival in the milieu of ROS reduction. While SOD was increased by UCP, CAT activity was enhanced when cells were challenged with H(2)O(2). UCP had no impact on H(2)O(2)-activated AKT, JNK, and p38 signaling but significantly decreased nuclear NF-κB levels. The overactivation of Nrf2 in response to oxidative stress was constrained by UCP. In conclusion, UCP protected endothelial cells against oxidative damage through intracellular ROS reduction, enhanced CAT activity, suppression of NF-kB, and prohibition of Nrf2 dysregulation. Thus, UCP might be a candidate for development of nutraceuticals against CVD and oxidative-related diseases and conditions.