Natural Aldose Reductase Inhibitor: Potential Therapeutic Agent for Eye DiseaseAuthor: Kun-Che Chang
1. Aldose Reductase (AR) Aldose reductase (AR, AKR1B1) is one of the aldo-ketoreductase super family proteins first reported in 1956 by H.G.Hers . AR is involved in the polyol pathway that converts glucose to sorbitol in a NADPH dependent manner . Level of AR is increased in the hyperglycemic condition and is considered a risk factor for diabetic complications. In the AR polyol pathway, induction of the Reactive Oxygen Species (ROS) is observed due to the consumption of NADPH and NAD+, which is important for neutralizing free radicals in the cell (Figure 1). The ROS that arose from AR therefore cause disease in a variety of organs. Increasing evidence has shown that AR is implicated in the inflammatory responses in the immune cells [3-7] and in the kidney [8,9]. Additionally, AR is a major factor that causes a variety of diabetic complications in the nerve [10-14] and in the heart [15-27]. Pharmacological inhibition of AR attenuates or delays these inflammatory responses and diabetic complications; therefore providing a valuable tool for investigating pathogenesis caused by endotoxin or diabetic hyperglycemia. In this perspective article, I will review two current reported natural compounds that show inhibitory effects on AR in vitro and in vivo that may carry therapeutic benefit against eye diseases.