Arctiin attenuates high glucose-induced human retinal capillary endothelial cell proliferation by regulating ROCK1/PTEN/PI3K/Akt/VEGF pathway in vitro.

Abstract

Diabetic retinopathy (DR) is one of the most prominent microvascular complications of diabetes, which remains the leading cause of legal blindness in the world. Arctiin, a bioactive compound from Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on a human retinal capillary endothelial cell (HRCEC) line and how arctiin inhibits cell proliferation in high glucose (HG)‐induced HRCECs. Results showed that arctiin decreased HG‐induced HRCECs proliferation in a dose‐dependent manner by inducing cell cycle arrest at the G0/G1 phase. Tube formation assay and immunofluorescence staining indicated that arctiin abrogated tube formation induced by HG‐induced HRCECs in a dose‐dependent manner via down‐regulation of VEGF expression. Mechanistic study indicated that perturbation of the ROCK1/PTEN/PI3K/Akt signalling pathway plays a vital role in the arctiin‐mediated anti‐proliferative effect. Furthermore, pre‐incubation of HRCECs with Y‐27632 attenuated arctiin‐induced cell cycle arrest, cell proliferation and tube formation inhibition. Y‐27632 also reversed the activation of PTEN, the inactivation/dephosphorylation of PI3K/Akt and down‐regulation of VEGF. Taken together, the results demonstrated that arctiin inhibits the proliferation of HG‐induced HRCECs through the activation of ROCK1 and PTEN and inactivation of PI3K and Akt, resulting in down‐regulation of VEGF, which inhibits endothelial cell proliferation.