The protective effects of fisetin in metabolic disorders: a focus on oxidative stress and associated events.

AbstractMetabolic syndrome is increasingly recognized as a significant precursor to various chronic diseases, contributing to a growing public health concern. Its complex pathogenesis involves multiple interrelated mechanisms, with oxidative stress identified as a cornerstone that exacerbates other pathogenic pathways. This study elucidates the molecular mechanisms by which oxidative stress intensifies metabolic disturbances, particularly insulin resistance. Some recent research has focused on fisetin, a natural product known for its potential benefits in diabetes and its associated microvascular and macrovascular complications. This paper compiles a comprehensive collection of findings by reviewing studies conducted over the past decade, detailing dosages, investigated markers, and their respective outcomes. Notably, a recurrent finding was fisetin's ability to enhance Nrf2, a principal regulator of antioxidant defense, in both metabolic and non-metabolic diseases. Furthermore, intriguing results suggest that the effects of Nrf2 extend beyond oxidative stress modulation, demonstrating favorable impacts on tissue-specific functions in metabolic regulation. This highlights fisetin not only as an antioxidant but also as a potential therapeutic agent for improving metabolic health and mitigating the effects of metabolic syndrome. In conclusion, fisetin can enhance the body's antioxidant defenses by modulating the Nrf2 pathway while also improving metabolic health through its effects on inflammation, cell survival, and energy metabolism, offering a comprehensive approach to managing metabolic disorders.Graphical abstract