Hyperoside improves diabetic retinopathy by regulating TGF-β1/miR-200b/VEGF pathway

Abstract Aims To evaluate the efficacy of hyperoside and the role of TGF-β1/miR-200b/VEGF pathway in treating diabetic retinopathy (DR). Methods (1) Retinal endothelial cells (RECs) were cultured in the normal-glucose group (NG), high-glucose group (HG), mannitol group, high glucose + low-concentration hyperoside group, high glucose + high-concentration hyperoside group, normal glucose + miR-200b inhibitor group (NG + MI), normal glucose + normal control group (NG + NC), high glucose + miR-200b mimic group (HG + MM), and high glucose + normal control group (HG + NC). The viability, migration and tube formation of RECs, and the expressions of TGF-β1, miR-200b and VEGF in each group were detected and compared. (2) Eight Sprague Dawley (SD) rats were used in the normal control group, and 32 SD rats established DR models were randomly divided into the four groups for DR group (DR), DR + low-dose hyperoside group, DR + high-dose hyperoside group, and DR + Calcium Dobesilate group. The tissue pathology and vasculopathy of rat retina, and the expressions of TGF-β1, miR-200b, and VEGF of retinal tissues in different group were tested and compared. Results (1) Excessive proliferation, migration and tube formation of RECs were induced by high glucose. The expressions of TGF-β1 and VEGF in HG were markedly up-regulated, but miR-200b levels were obviously down-regulated. However, hyperoside could significantly reverse the expressions of TGF-β1, VEGF and miR-200b; and inhibit high-glucose-induced over-proliferation of RECs dose-dependently. RECs viability and VEGF level were much higher in NG + MI than for NG but lower in HG + MM than for HG, while miR-200b level was substantially lower in NG + MI than for NG but higher in HG + MM than for HG. (2) The retinal pathological changes and vasculopathy in DR rats were more serious compared with normal rats. TGF-β1 and VEGF levels in DR rats retina were markedly up-regulated, while miR-200b levels were obviously down-regulated. However, hyperoside could notably reverse the expressions of TGF-β1, VEGF, and miR-200b in DR rat retina and alleviate retinal tissue injury and vascular lesions of DR rats dose-dependently. Conclusion Hyperoside could treat DR by regulating TGF-β1/miR-200b/VEGF pathway.