Melatonin’s role in redox homeostasis: A preclinical and clinical perspective

Abstract

Melatonin is a phylogenetically ancient molecule with diverse biological activities, including anti-inflammatory and redox properties. Although its role as an antioxidant is well-established, the broader impact of melatonin on redox signaling pathways still needs to be explored. This review addresses this gap by providing an overview of melatonin's known mechanisms of action in major redox signaling pathways, such as Nrf2, NF-kB, and FoxO, as well as its involvement in epigenetic processes and the ubiquitin-proteasome system. The review also explores melatonin’s potential as a therapeutic agent in various pathological conditions, including cancer, Alzheimer’s disease, diabetes, and cardiomyopathy. Finally, we discuss recent clinical trials that underscore melatonin’s role in modulating hormesis-related redox signaling, suggesting its utility as a therapeutic adjuvant in diseases characterized by oxidative or inflammatory damage.