Anti- and pro-oxidant properties of polyphenols and their role in modulating glutathione synthesis, activity and cellular redox potential: Potential synergies for disease management

Cellular metabolic activities are controlled by pathways catalyzed by enzymes, closely regulated by signal transduction through induction or inhibition processes. Metabolic disorders and cellular dysregulation are often linked to redox-dependent signaling in a complex relationship. Glutathione (GSH) and polyphenols which are known regulators of cellular redox homeostasis have been studied immensely. However, no study has considered their potential interactions and synergies as novel mechanisms to control cellular disorders. GSH does not only act as an antioxidant, but as a ligand that binds to inactivate enzymes and toxins. Also, depending on cellular environment, structure, pH, concentration and availability of transition metals of high charge density, polyphenols may possess either anti-oxidant or pro-oxidant properties. Owing to their remarkable influence on cellular redox potential and metabolic signaling as individual compounds, this study considered the potential interactions and synergies between GSH and polyphenols in disease management. Generally, both GSH and polyphenols reduce oxidative stress in normal cells and may under exacerbating conditions of low GSH/GSSG ratio, induce apoptotic mechanisms in abnormal cells. Investigating the effects of pH, polyphenol and GSH concentrations, availability of transition metals, caloric restriction and polyphenol structure on apoptosis and proliferation in cancer cells in the future may be a basis for the synergistic exploitation of GSH and polyphenols in disease management.