Intestinal polyphenol antioxidant activity involves redox signaling mechanisms facilitated by aquaporin activity

Abstract

Ascertaining whether dietary polyphenols evoke an antioxidant or prooxidant activity, which translates to a functional role required to maintain intestinal cell homeostasis continues to be an active and controversial area of research for food chemists and biochemists alike. We have proposed that the paradoxical function of polyphenols to autoxidize to generate H2O2 is a required first step in the capacity of some plant phenolics to function as intracellular antioxidants. This is based on the fact that cell redox homeostasis is achieved by a balance between H2O2 formation and subsequent outcomes of antioxidant systems function. Maintaining optimal extracellular and intracellular H2O2 concentrations is required for cell survival, since low levels are important to upregulate endogenous antioxidant capacity; whereas, concentrations that go beyond homeostatic control typically result in an inflammatory response, growth arrest, or eventual cell death.Aquaporins (AQPs) are a family of water channel membrane proteins that facilitate cellular transportation of water and other small molecule-derived solutes, such as H2O2, in all organisms. In the intestine, AQPs act as gatekeepers to regulate intracellular uptake of H2O2, generated from extracellular polyphenol autoxidation, thus enabling an intracellular cell signaling responses to mitigate onset of oxidative stress and intestinal inflammation.In this review, we highlight the potential role of AQPs to control important underlying mechanisms that define downstream regulation of intestinal redox homeostasis, specifically. It has been established that polyphenols that undergo oxidation to the quinone form, resulting in subsequent adduction to a thiol group on Keap1-Nrf2 complex, trigger Nrf2 activation and a cascade of indirect intracellular antioxidant effects. Here, we propose a similar mechanism that involves H2O2 generated from specific dietary polyphenols with a predisposition to undergo autoxidation. The ultimate bioactivity is regulated and expressed by AQP membrane function and thus, by extension, represents expression of an intracellular antioxidant chemoprotection mechanism.