Fig. 2. Resveratrol inhibited hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) via the PI3K/Akt pathway. ARPE-19 cells in complete medium were pretreated with 10 µmol/L, 50 µmol/L, and 100 µmol/L resveratrol for 1 hour, and then exposed to normoxia or hypoxia for 16 hours. Resveratrol significantly reduced VEGF protein and mRNA levels as determined by ELISA (A) and RT-PCR (B) in a dose-dependent manner. (C) Pretreatment with resveratrol in varying concentration abrogated the hypoxia-induced HIF-1α protein accumulation in a dose-dependent manner. (D) Pretreatment with resveratrol resulted in decrease of phospho-Akt (p-Akt) and phospho-mTOR (p-mTOR) levels in a dose-dependent manner. ^*p<0.0001 vs. the normoxia group, ^†p<0.001 vs. the hypoxia group. ELISA, Enzyme-Linked Immunosorbent Assay.