Extensive research within the last two decades revealed that most chronic illnesses, including cancer, neurological, autoimmune
and cardiovascular diseases are mediated through chronic inflammation. Thus, suppressing chronic inflammation has the
potential to delay, prevent, and treat those diseases. However, side effects and high costs of current anti-inflammatory drugs force the
development of new drugs.
Natural products represent an important source of new bioactive compounds. Among them, phenolic compounds, which are widely
distributed in plants, have been described as having many therapeutic effects. Several reviews have addressed the anti-inflammatory
activity of phenols, attributing their properties not only to the antioxidant capacity, but also to inflammatory mediators’ modulation,
namely cytokines and pro-inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase-2.
Signal transduction pathways precede changes in inflammatory mediators’ expression. However, only a restricted number of studies have
addressed the effect of phenols on a specific signal transduction pathway. The present review attempts to summarize and highlight a
broad range of inflammation-associated signaling pathways modulated by phenols namely: nuclear factor (NF)-κB, activator protein
(AP)-1, peroxisome proliferator-activated receptor (PPAR) and nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factors;
mitogen-activated protein kinases (MAPKs); protein tyrosine kinases (PTKs); tyrosine phosphatidylinositol 3-kinase (PI3K)/Akt and
ubiquitin-proteasome system. As a consequence of phenols effect on signaling pathways, described above, their action on inflammatory
mediators’ production is mentioned. Finally, it is established that the structure-activity relationships of phenolic compounds are a
valuable information source on the development of new anti-inflammatory drugs from natural products.