Metabolic memory and diabetic nephropathy: Beneficial effects of natural epigenetic modifiers

Nephropathy is one of the most frequent complications of chronic diabetes. The main reason for nephropathy despite being hyperglycemia, but it progresses even after good glycemic control has been achieved in diabetic patients. The effects of prior exposure to high blood glucose conditions depend upon the severity and duration of this exposure, indicating a "metabolic memory" phenomenon. Hyperglycemia not only increases oxidative stress but is also alleged to start several biochemical anomalies and alter gene expression associated with metabolic homeostasis. High glucose levels induce epigenetic modifications that alter gene expression without changing DNA sequences. These epigenetic modifications have shown to be reversible and have the potential to cease adverse effects if good glycemic control is achieved from initiation of diabetes. However, if good glycemic control is not achieved for months, these modifications stand firm to reversals. Therapies and drugs have been in use to prevent epigenetic modifications and oxidative stress, which also helped in ameliorating diabetic nephropathy. But these synthetic drugs are loaded with side effects like increased body weight, kidney dysfunction etc. So phytochemicals are emerging as alternatives and many of them have already been used to treat nephropathy. But still, there is rigorous need to evaluate phytochemicals which can regulate epigenetic events and have the potential to decelerate the further progression of these life-threatening diseases. In this review article we discuss the potential epigenetic modifiers from plants that can erase metabolic memory and can thus be protective against diabetic nephropathy.