Exploring the links between polyphenols, Nrf2, and diabetes: A review

Diabetes mellitus, a complex metabolic disorder, is marked by chronic hyperglycemia that drives oxidative stress and inflammation, leading to complications such as neuropathy, retinopathy, and cardiovascular disease. The Nrf2 pathway, a key regulator of cellular antioxidant defenses, plays a vital role in mitigating oxidative damage and maintaining glucose homeostasis. Dysfunction of Nrf2 has been implicated in the progression of diabetes and its related complications. Polyphenols, a class of plant-derived bioactive compounds, have shown potential in modulating the Nrf2 pathway. Numerous compounds have been found to activate Nrf2 through mechanisms including Keap1 interaction, transcriptional regulation, and epigenetic modification. Preclinical studies indicate their ability to reduce reactive oxygen species (ROS), improve insulin sensitivity, and attenuate inflammation in diabetic models. Clinical trials with certain polyphenols, such as resveratrol, have demonstrated improvements in glycemic parameters, though results remain inconsistent. While polyphenols show promise as a component of non-pharmacological approaches to diabetes management, challenges such as bioavailability, individual variability in response, and limited clinical evidence highlight the need for further investigation. Continued research could enhance understanding of their mechanisms and improve their practical application in mitigating diabetes-related complications.