Epigallocatechin-3-gallate protects retinal vascular endothelial cells from high glucose stress in vitro via the MAPK/ERK-VEGF pathway

Abstract

ABSTRACT. Diabetic retinopathy (DR) is a frequent microvascular complication of diabetes, and one of the most common causes of legal blindness in the world. Epigallocatechin-3-gallate (EGCG) produces an anti-oxidative and anti-inflammatory effect against various human diseases. In this study, we determined the effect of EGCG on a human retinal endothelial cell (HREC) line. The cell viability was determined by a standard MTT assay, while the cell cycle and apoptosis rate were analyzed by flow cytometry. Inflammatory marker expression was detected by enzyme-linked immunosorbent assay. Treatment of HRECs with EGCG (20 and 40 mM) led to a significant decrease in the apoptosis rate (2.35 ± 0.56 and 1.24 ± 0.32%). The culture supernatant of cells treated with high glucose concentrations showed significantly higher levels of TNF-a (598.7 ± 89.7 vs 193.2 ± 38.5 pg/ mL; P < 0.001), IL-6 (6.16 ± 0.51 vs 1.61 ± 0.21 ng/mL; P < 0.001), and ICAM-1 (31.6 ± 4.4 vs 14.8 ± 2.9 ng/mL; P < 0.001) compared to the cells in the control group. EGCG decreased the expression level of phosphorylated p38-mitogen activated protein kinase (MAPK) and extracellular regulated kinase (ERK)1/2. Moreover, EGCG was shown to significantly inhibit the expression of vascular endothelial growth factor (VEGF). Therefore, EGCG treatment ameliorated the negative effect of high glucose concentrations on the cell viability and apoptotic rate. The protective effects of EGCG under high glucose conditions may be attributed to the regulation of inflammatory cytokines and inhibition of the MAPK/ERK-VEGF pathway.

The potential health benefits of dietary natural plant products in age related eye diseases

“…(2014) Epigallocatechin gallate 20 and 40 mM Human retinal endothelial cell Inhibits expression of vascular endothelial growth factor (VEGF) and reduces negative impact of high glucose concentration on the cell viability. Prevents diabetic retinopathy Zhang et al. (2016) Epigallocatechin gallate 1–200 μM Sprague-Dawley rats Inhibits cell proliferation and reduces vascular leakage and permeability in VEGF.…”

Pterostilbene Prevents Early Diabetic Retinopathy Alterations in a Rabbit Experimental Model

“…Thus, for example, a protective effect has been observed for DR and other retinopathies with resveratrol [23][24][25], epigallocatechin gallate [26,27], curcumin [28,29] and quercetin [30,31], among others. Their actions have been attributed to their capacity to modulate different molecular targets, including sirtuins like SIRT1 [32], kinases such as MAPK [33][34][35], transcription factors like Nrf2/ARE [36,37], nuclear factor kappa B (NF-kB) [34] and others that provide antioxidant and anti-inflammatory protection [3]. We have demonstrated the protector effect of Pter as an antioxidant in different experimental models [38].…”

The Effect and Mechanism of TRPC1, 3, and 6 on the Proliferation, Migration, and Lumen Formation of Retinal Vascular Endothelial Cells Induced by High Glucose

“…In the vitreous and retinal tissues of patients with PDR, VEGF gene, and protein expression levels are significantly increased and are closely related to retinal neovascularization [34]. Previous experiments have shown that in addition to the common cognitive VEGF AKT-inositol 1,4,5-trisphosphate pathway and PLC-γ-MAPK (including inositol 1,4,5-trisphosphate), VEGF is also involved in the expression of NF-κB and the activation of TRPC channels, regulating angiogenesis [35].…”