Mulberry Extract Mitigates Glucose‐Induced Oxidative Injury in Differentiated ARPE‐19 Cells by Enhancing Antioxidant Defense: Implications for Diabetic Retinopathy

Diabetic retinopathy, or DR, is an eye disease that causes globally impaired vision and vision loss among working-age adults. The progression of DR is related to persistent metabolic disturbances resulting from hyperglycemia. In diabetic patients, retinal cells, including RPE, are continuously exposed to high glucose conditions, which trigger oxidative stress and injury and finally lead to DR. Mulberry is rich in phytochemicals that offer various health benefits and is a significant source of anthocyanins, known for their antioxidant properties. Our research aimed to assess the antioxidant effects and underlying mechanisms of mulberry extract (ME) on high glucose-induced oxidative injury in human retinal (differentiated ARPE-19) cells. Differentiated ARPE-19 was treated with ME at 5, 50, and 500 μg/mL for 24 h, followed by incubating with 25 mM glucose for 48 h. From the HPLC analysis, ME contained anthocyanin compounds, including C3G and C3R, at 8.13 and 9.86 mg/g of dry weight, respectively. ME could prevent differentiated ARPE-19 cells from oxidative injury by mitigating ROS generation, modulating protein expression in the apoptosis markers (Bax, cytochrome <i>c</i>, Bcl-2, caspase-9, and -3), and enhancing the capacities of intracellular antioxidants by activating the critical transcription factor Nrf2 in a dose-response relationship. Additionally, ME could boost the ability of the intracellular antioxidant system of human retina cells in normal conditions. However, this study is only a cell culture study. Thus, the health benefits of mulberry, especially eye health and vision, and preventive measures against DR should be further evaluated in animals and humans.