Polyphenols by Generating H2O2, Affect Cell Redox Signaling, Inhibit PTPs and Activate Nrf2 Axis for Adaptation and Cell Surviving: In Vitro, In Vivo and Human Health

Abstract

Human health benefits from different polyphenols molecules consumption in the diet, derived mainly by their common activities in the gastrointestinal tract and at the level of blood micro-capillary. In the stomach, intestine and colon, polyphenols act as reducing agents preventing lipid peroxidation, generation and absorption of AGEs/ALEs (advanced glycation end products/advanced lipid oxidation end products) and postprandial oxidative stress. The low absorption of polyphenols in blood does not support their activity as antioxidants and their mechanism of activity is not fully understood. The results are from in vitro, animal and human studies, detected by relevant oxidative stress markers. The review carries evidences that polyphenols, by generating H2O2 at nM concentration, exogenous to cells and organs, act as activators of signaling factors increasing cell Eustress. When polyphenols attain high concentration in the blood system, they generate H2O2 at µM concentration, acting as cytotoxic agents and Distress. Pre-treatment of cells or organisms with polyphenols, by generating H2O2 at low levels, inhibits cellular PTPs (protein tyrosine phosphatases), inducing cell signaling through transcription of the Nrf2 (nuclear factor erythroid 2-related factor 2) axis of adaptation and protection to oxidation stress. Polyphenols ingestion at the right amount and time during the meal acts synergistically at the level of the gastrointestinal tract (GIT) and blood system, for keeping the redox homeostasis in our organism and better balancing human health.

Modulation of Renal Function in a Metabolic Syndrome Rat Model by Antioxidants in Hibiscus sabdariffa L.

“…In this sense, H 2 O 2 can have a dual effect by modulating vascular reactivity, and by a vasodilator effect in the sub mucosal arterioles [ 39 ]. Therefore, the effect depends on the vascular bed in which it is acting [ 40 ] and upon the physiological and pathological conditions [ 41 ]. The effect also depends on the concentration; at 10–100 nM, it has beneficial effects on the vascular reactivity; however, at high concentrations of 1 µM it induces vasoconstriction, inflammation, and cell death [ 42 ].…”

“…A recent study showed that the beneficial effect of the polyphenols present in HSL can be due to a lower generation of H 2 O 2 in the arterioles. H 2 O 2 interacts exogenously with endothelial cell, and penetrates through aquaporins inhibiting phosphatases, NADPH oxidases and activating Nrf2 [ 41 ]. However, the increase in the activity of the SOD isoforms could lead to an increase in the endogenous H 2 O 2 in the kidney.…”

In Vitro Evaluation of Pro- and Antioxidant Effects of Flavonoid Tricetin in Comparison to Myricetin

“…ROS levels are regulated by various enzymatic and non-enzymatic mechanisms. The latter involves also low-weight molecules with pronounced redox properties, such as polyphenols, ascorbic acid, tocopherols, and carotenoids [ 2 , 3 ]. While human beings can biosynthesize some low-weight redox-active molecules, such as kynurenines [ 4 ], the majority of the required antioxidants, ascorbic acid or polyphenols amongst others, needs to be taken up from food [ 4 ].…”

Coffee and Lower Risk of Type 2 Diabetes: Arguments for a Causal Relationship

“…Phytochemicals may also indirectly activate the Nrf2/Keap1 system by increasing the intracellular levels of oxygen radical species or nitric oxide all of which target cysteine residues of Keap 1. Free oxygen radical species including H 2 O 2 may be either generated directly by phenolics extra- or intracellularly, in the presence of Cu(II) or Fe(III) ions [ 55 , 56 , 60 , 93 , 94 ], or may come from mitochondria [ 95 , 96 , 97 , 98 , 99 , 100 ].…”