TY - JOUR AB - Diabetic retinopathy (DR) is a microvascular complication of diabetes, while retinal endothelial cell (REC) dysfunction is considered the primary pathological process of DR. Naringenin, a natural flavonoid compound, exhibits therapeutic potential against multiple types of endothelial cell injury. To the best of our knowledge, however, its effect on REC injury has not been previously investigated. Therefore, the aim of the present study was to investigate the effect of naringenin on high glucose (HG)‑induced REC injury and assess the underlying mechanism. To establish a retinal injury model, human (H)RECs were treated with 30 mM glucose. Cell Counting Kit‑8 assay and TUNEL staining were used to assess the effects of naringenin on cell proliferation and apoptosis, respectively. Reactive oxygen species (ROS) levels and concentration of tetrahydrobiopterin (BH4), the essential cofactor of endothelial nitric oxide synthase (eNOS), were measured using a ROS detection kit and ELISA, respectively. The transfection efficiency of HRECs with guanosine triphosphate cyclohydrolase‑1 (GTPCH1) interfering plasmid was examined by reverse transcription‑quantitative PCR. The protein expression levels of Ki67, proliferative cell nuclear antigen (PCNA), eNOS and GTPCH1 were determined by western blot analysis. Compared with the HG‑induced group alone, co‑treatment with naringenin inhibited HG‑induced HREC apoptosis in a dose‑dependent manner, increased expression levels of the proliferation‑associated proteins Ki67 and PCNA and effectively decreased intracellular ROS levels. Furthermore, naringenin upregulated GTPCH1/eNOS signaling and promoted release of BH4. However, GTPCH1 knockdown partially reversed the ameliorative effect of naringenin on HG‑induced HREC injury. In summary, the present study suggested that naringenin effectively inhibited HG‑induced HREC apoptosis and intracellular oxidative stress, which may be associated with naringenin‑mediated GTPCH1/eNOS upregulation. AD - Health Management Center of Dalian Second People's Hospital, Dalian, Liaoning 116011, P.R. China Medical Department of Dalian Second People's Hospital, Dalian, Liaoning 116011, P.R. China AU - Xue,Bing AU - Wang,Yu DA - 2022/06/01 DO - 10.3892/etm.2022.11355 IS - 6 JO - Exp Ther Med KW - naringenin apoptosis diabetic retinopathy guanosine triphosphate cyclohydrolase‑1/endothelial nitric oxide synthase PY - 2022 SN - 1792-0981 1792-1015 SP - 428 ST - Naringenin upregulates GTPCH1/eNOS to ameliorate high glucose‑induced retinal endothelial cell injury T2 - Experimental and Therapeutic Medicine TI - Naringenin upregulates GTPCH1/eNOS to ameliorate high glucose‑induced retinal endothelial cell injury UR - https://doi.org/10.3892/etm.2022.11355 VL - 23 ER -