Table 2.

Effects of flavanols on cellular and molecular mechanisms affected by diabetic retinopathy.

Name of Substances/Compound	Dose	Model	Observations	Reference
(−)—Epicatechin	50 and 100 mg/kg for 2 weeks	Unmodified rat serum albumin and AGE-modified rat serum albumin intravenous injected (normoglycemic) rats	↑ AGE breaking activity	[62]
			↓ AGE burden and vascular apoptosis
	10, 25, 50, 100, 250, 500 and 1000 μg/mL	Collagen–glycated bovine serum albumin complexes and glycated human serum albumin	↑ AGE breaking activity
Epigallocatechin	2, 20 and 200 µg	Balb/c mice intradermally injected with NPDR patients serum	↓ angiogenic effects	[63]
Green tea	5.7 g/kg for 12 weeks	STZ-induced T1DM rats	↓ occludin, NMDAr1 subunit and GLAST levels	[65]
			↓ BRB breakdown
			↓ impaired electroretinography recordings
			↓ GFAP, oxidative retinal markers and glutamine synthetase levels
	1, 10 or 100 µg/mL	High glucose-exposed PRRMC, rMC-1 and ARPE-19 cells	↑ GSH, GLAST and NMDAR1 protein levels
			↓ ROS and glutamine synthetase
			↓ claudin-1 levels
	100 mL for 12 months	STZ-induced T1DM rats	↓ superoxide production, acellular capillaries and pericyte ghosts	[66]
Epigallocatechin gallate	2, 20 and 200 µg/mL	Balb/c mice intradermally injected with NPDR patients serum	↓ angiogenic effects	[63]
	200 mg/kg orally administered for 4 days	VEGF intradermally injected Balb/c mice and Sprague-Dawley rats	↓ vascular leakage and permeability by BRB breakdown	[67]
	1, 10, 25 and 50 μM for 1.5, 24 or 72 h	TPA and TNF-α-exposed HRPECs and ARPE-19 cells	↓ MMP-9 levels
			↓ cell death and MMP-9, VEGF and VEGF Receptor-2 mRNA expression
		H2O2-exposed ARPE-19 cells
			↓ ROS levels
		VEGF-exposed HRMECs	↓ cell proliferation, vascular permeability and tube formation
Catechin	50, 100 and 200 mg/kg by intravitreal injection for 8 weeks	STZ-induced diabetic rats	↑ HSP27 levels	[68]
			↓ IL-1β, IL-6 and TNF-α levels
			↓ NF-κB pathway

AGE: advanced glycation end products, ARPE-19: human retinal pigment epithelial cell line, Balb/c: Bagg’s albino C mice substrain, BRB: blood–retinal barrier, GFAP: glial fibrillary acidic protein, GLAST: glutamate aspartate transporter 1, GSH: glutathione, H₂O₂: hydrogen peroxide, HRMECs: human retinal microvascular endothelial cells, HRPECs: human retinal pigment epithelial cells, HSP27: heat shock protein 27, IL-1β: interleukin-1β, IL-6: interleukin-6, MMP-9: metalloproteinase-9, NF-κB: nuclear factor kappa-B, NMDAr1: NR1 subunit of N-methyl-D-aspartate receptor, NPDR: non-proliferative diabetic retinopathy, PRRMC: primary rat retina Müller cells, rMC-1: transformed rat retinal Müller cell line, ROS: reactive oxygen species, STZ: streptozotocin, T1DM: type 1 diabetes mellitus, TNF-α: tumor necrosis factor alfa, TPA: 12-O-tetradecanoylphorbol-13-acetate, VEGF: vascular endothelial growth factor, ↑: increase, ↓ decrease.