sincalide and epigallocatechin-gallate

Diabetic retinopathy (DR) is a neurovascular complication of diabetes mellitus that leads to blindness in the working-age population. Retinal Müller cells proliferate and produce pro-angiogenic factors, including vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via the reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome axis to promote proliferative DR. Epigallocatechin-3-gallate (EGCG) plays anti-oxidant, anti-inflammatory, anti-proliferative and anti-angiogenic roles in Müller cells. A prodrug of EGCG (pro-EGCG) enhances the bioavailability of EGCG. In an in vitro model of high glucose-stimulated Müller cells, pro-EGCG inhibited proliferation and pro-angiogenic factor production by down-regulating the activity of the ROS/TXNIP/NLRP3 inflammasome axis. In a mouse DR model, pro-EGCG reduced ROS accumulation, NLRP3 inflammasome activation, Müller cell proliferation, and production of the pro-angiogenic factors VEGF and HGF. In summary, pro-EGCG mitigated hyperglycaemia-challenged Müller cell proliferation and pro-angiogenic factor production by inhibiting ROS/TXNIP/NLRP3 inflammasome signalling, implying a potential therapeutic strategy for DR.

Topics: Angiogenesis Inducing Agents; Animals; Blotting, Western; Carrier Proteins; Catechin; Cell Count; Cell Proliferation; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Ependymoglial Cells; Glucose; Inflammasomes; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Prodrugs; Reactive Oxygen Species; Sincalide; Superoxide Dismutase; Thioredoxins; Transfection

To investigate the effect and mechanism of EGCG on the proliferation and invasion of human hepatioma HepG2 cell.. Hepatioma HepG2 cell was treated with EGCG at different concentrations. The effect of EGCG on HepG2 proliferation was examined by CCK-8. The apoptosis of HepG2 treated with EGCG was observed by fluorescence microscopy and FCM via Annexin V-FITC/PI staining. The invasion of HepG2 was detected by Transwell assay. The expression of MMP-2 and VEGF was analyzed by ELISA.. HepG2 proliferation was inhibited after treated with EGCG. The IC25 of 24 h and 48 h was 58.19 and 54.19 mg/L. The IC50 of 24 h and 48 h was 133.90 and 78.97 mg/L. The apoptosis of HepG2 was induced significantly after treated with 60 and 135 mg/L EGCG, and the number of cells crossing Matrigel membrane was (28.33+/-7.66) and 0 (P<0.05), and the inhibitory rate of invasion was 69.47% and 100%. The expression of MMP-2 and VEGF decreased significantly.. EGCG suppressed the proliferation and invasion of HepG2 with the possible mechanism of inducing apoptosis and down-regulating the expression of MMP-2 and VEGF in HepG2.

Topics: Antineoplastic Agents; Apoptosis; Catechin; Cell Proliferation; Hep G2 Cells; Humans; Matrix Metalloproteinase 2; Neoplasm Invasiveness; Sincalide; Vascular Endothelial Growth Factor A