Therapeutic Effects of Natural Products in Diabetic Retinopathy through Aldose Reductase Inhibition

Diabetic retinopathy (DR) is one of the most dangerous and cruel microvascular complications of diabetes, leading to visual impairment and blindness if left untreated. The development of DR is determined by complex multiple pathologic mechanisms, including oxidative stress, chronic inflammation, retinal vascular dysfunction, and retinal neuronal damage. Aldose reductase (AR) activation in the polyol pathway has been implicated to lead to excessive accumulation and production of reactive oxygen species (ROS) in several tissues (e.g., the heart, vasculature, kidney, and eye) under acute and chronic diabetic conditions. Therefore, many research scientists have extensively focused on developing synthetic AR inhibitors or finding AR inhibitors from natural products. Natural products and their bioactive compounds have been an important source of potential drugs to alleviate pathological conditions in various metabolic diseases. They are considered more effective, economical, convenient, and relatively safe. This review article aimed to focus on summarizing the therapeutic potential of natural product-based AR inhibitors for DR management. Many dietary compounds and phytochemicals have been found to be a good source of promising AR inhibitors. Their antioxidant effects can be used as a promising adjunctive treatment to conventional treatment (e.g., anti-vascular endothelial growth factor therapy) for DR management. Our comprehensive narrative review guides future research in drug discovery and development to modulate pathologic DR conditions.