**5. Conclusion**

The potential for polyphenols to be used therapeutically appears more probable as more research is completed. Additionally, the benefits likely cross into multiple disease states with positive effects for them all. Pro-inflammatory transcription factor NF-κβ is inhibited by binding of polyphenols, thus limiting the expression of harmful inflammatory factors. Similarly, NF-κβ activity can also be blocked by limiting its activation via the signaling pathway. While limiting NF-κβ activity limits inflammation, activating the positive transcription factor Nrf2 increases expression of enzymes protective of oxidative damage. Studies demonstrate that polyphenols activate Nrf2.

From a metabolic perspective, limiting inflammation is also ideal, thus overlapping benefits are observed from the anti-inflammatory effects described when considering metabolic dysfunction. Limitation of NF-κβ activity provides a protective effect against the inflammatory state caused by obesity. Polyphenols have also been shown to improve insulin sensitivity and metabolic regulation by modifying the level of acetyl-coA directly. Levels of acetyl-coA strongly determine the activity of acetyl-coA carboxylase which can regulate metabolic flux. Polyphenols also affect the expression of acetyl-coA carboxylase by altering the activity of histone acetyltransferase (HAT) enzymes. These enzymes along with histone deacetylase enzymes (HDAC) appear sensitive to polyphenol interaction and are responsible for epigenetic reprogramming that alter gene expression level. Modifications at the epigenetic level offer re-regulation of metabolism.

A role in cancer prevention and adjective therapy also emerges as studies show that epigenetic modifications by polyphenols can limit expression of tumor growth proteins while protecting cells from oxidative damage by traditional therapies. Much of this effect is also due to the limited activity of NF-κβ and activation of Nrf2 that was described previously. Limiting inflammatory proteins while also protecting against oxidative damage reduces the risk of DNA damage that could develop into cancer. In addition to the effects on HATs and HDACs, polyphenols have also been shown to affect DNA methyltransferase (DNMT) activity. These enzymes,

#### *Therapeutic Potential of Dietary Polyphenols DOI: http://dx.doi.org/10.5772/intechopen.99177*

responsible for methylation and demethylation of DNA, are inhibited by polyphenols in general and can limit the methylation level at a gene promoter, thus allowing its expression. One such study showed higher levels of methylation at the BRCA1 gene promoter resulting in decreased expression and shorter interval before disease return. Treatment with catechin polyphenols limited the methylation of BRCA1 and increased disease free intervals. Early studies of adjunctive therapies with polyphenols demonstrate a potential for polyphenols mediated transition metal increased oxidative damage to the cancer cells that can overcome the cancerous cells' increased ability to handle oxidative stress and therefore achieve cell death. There is still much to be studied regarding this pro-oxidant effect of transition metal interaction with polyphenols, but the potential to target cancer cells more directly is encouraging.

A summary of the potential for polyphenols to be used to reduce inflammatory markers, particularly the one associated with a most negative outcome, are suppressed with the addition of certain polyphenols. An overlap exists between the suppression of inflammatory factors and the potential for metabolic re-regulation. In addition to the effects on metabolic regulation achieved by decreasing inflammation, polyphenols also offer improved support of metabolic regulation via metabolic enzyme control and transcription factor mediation. Epigenetic effects cross over between metabolic control and anti-cancer potential, demonstrating again the potential for multi-targeted benefits.
