Intracellular Signaling Pathways Modulated by Phenolic Compounds: Application for New Anti-Inflammatory Drugs Discovery
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.
Keywords: Cytokines; chemokines; drug discovery; flavonoids; inflammation; intracellular signaling pathways; mitogen-activated protein kinase; natural compounds; nitric oxide; phenolic compounds; proteasome; structure-activity relationship; transcription factor
Document Type: Research Article
Affiliations: Centro de Estudos Farmaceuticos, Faculdade de Farmacia, Universidade de Coimbra, Polo das Ciencias da Saude, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
Publication date: 2012-06-01
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