Intracellular Signaling Pathways Modulated by Phenolic Compounds: Application for New Anti-Inflammatory Drugs Discovery
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.
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