Epigallocatechin Gallate (EGCG) Improves Anti-Angiogenic State, Cell Viability, and Hypoxia-Induced Endothelial Dysfunction by Downregulating High Mobility Group Box 1 (HMGB1) in Preeclampsia

Abstract

Background Preeclampsia (PE) is a serious complication of pregnancy with no effective therapy. This study assessed whether epigallocatechin gallate (EGCG) could reduce the production of anti-angiogenic factors, improve cell viability, and suppress endothelial dysfunction in vitro via regulating high mobility group box 1 (HMGB1) in preeclampsia. Material/Methods Human umbilical vein endothelial cells (HUVECs) grown in conditioned medium from hypoxic JEG-3 cells were used to investigate the effects of EGCG on anti-angiogenic state, cell viability, and markers of endothelial dysfunction. To confirm that EGCG exerted its effects via HMGB1, we also examined the impact of EGCG on anti-angiogenic state, cell viability, and endothelial dysfunction following HMGB1 treatment in vitro . Results EGCG inhibited HMGB1 expression in hypoxic trophoblast cells in a dose-dependent manner. In addition, EGCG relieved anti-angiogenic state and endothelial dysfunction in hypoxic trophoblast cells by downregulating HMGB1. Moreover, EGCG dose-dependently promoted cell proliferation by downregulating HMGB1. Conclusions Taken together, our data show the protective role of EGCG in preeclampsia and revealed EGCG-mediated effects on the production of anti-angiogenic factors, cell viability, and endothelial dysfunction through downregulating HMGB1. These observations suggest that EGCG is a novel therapeutic candidate for preeclampsia.

The Changes in Antioxidant Activity of Selected Flavonoids and Caffeine Depending on the Dosage and Form of Thiamine

“…In our study, it was confirmed that samples with EGCG usually showed the highest antioxidant activity. Previous studies also confirm that among all flavonoids, EGCG demonstrated the highest free radicals scavenging efficacy [46,[53][54][55]. According to Dicson due to the fact that EGCG had the strongest ability at scavenging free radicals by multiple substrates and thus reduces the risk of neurodegenerative diseases [56].…”

EGCG, a Green Tea Compound, Increases NO Production and Has Antioxidant Action in a Static and Shear Stress In Vitro Model of Preeclampsia

“…In one study, the administration of EGCG capsules to PE patients using hydralazine, an antihypertensive drug for controlling hypertensive crises, reduced the necessary doses of the drug, as well as the interval between doses [23]. Additionally, an in vitro study of EC exposed to hypoxia demonstrated that EGCG improved endothelial dysfunction parameters and the anti-angiogenic state [21].…”

“…In addition to directly sequestering reactive oxygen species (ROS), EGCG increases the bioavailability of NO through the activation of eNOS via PI3K and may help in the treatment of several cardiovascular and metabolic diseases [17][18][19][20]. However, studies showing the effect of EGCG in the PE context are limited, and none use the experimental model of this study [21][22][23].…”

Effects of Antioxidant Intake on Fetal Development and Maternal/Neonatal Health during Pregnancy

“…Although there is insufficient evidence of the effect of EGCG on PE in humans or in animal models (with no studies in the latter), it has recently been shown that EGCG exerts a protective role against endothelial dysfunction and enhances the anti-angiogenic status in hypoxic trophoblast cells. The protective effect of EGCG appears to be due, in part, to the inhibition of the expression of the high mobility group box 1 (HMGB1), a late inflammatory factor released by trophoblasts during hypoxia that induces endothelial damage [45]. In addition, the authors observed that this antioxidant significantly increased cell viability under hypoxic conditions.…”