Abstract: This review offers a systematic understanding about how polyphenols target multiple
\ninflammatory components and lead to anti-inflammatory mechanisms. It provides a clear
\nunderstanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate
\nimmunity by interfering with immune cell regulation, proinflammatory cytokines\u2019 synthesis, and
\ngene expression. They inactivate NF-\u03baB (nuclear factor kappa-light-chain-enhancer of activated
\nB cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways.
\nPolyphenolic compounds inhibit phosphatidylinositide 3-kinases\/protein kinase B (PI3K\/AkT),
\ninhibitor of kappa kinase\/c-Jun amino-terminal kinases (IKK\/JNK), mammalian target of rapamycin
\ncomplex 1 (mTORC1) which is a protein complex that controls protein synthesis, and JAK\/STAT.
\nThey can suppress toll-like receptor (TLR) and pro-inflammatory genes\u2019 expression. Their antioxidant
\nactivity and ability to inhibit enzymes involved in the production of eicosanoids contribute as well to
\ntheir anti-inflammation properties. They inhibit certain enzymes involved in reactive oxygen species
\nROS production like xanthine oxidase and NADPH oxidase (NOX) while they upregulate other
\nendogenous antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione (GSH)
\nperoxidase (Px). Furthermore, they inhibit phospholipase A2 (PLA2), cyclooxygenase (COX) and
\nlipoxygenase (LOX) leading to a reduction in the production of prostaglandins (PGs) and leukotrienes
\n(LTs) and inflammation antagonism. The effects of these biologically active compounds on the
\nimmune system are associated with extended health benefits for different chronic inflammatory
\ndiseases. Studies of plant extracts and compounds show that polyphenols can play a beneficial role inprevention and the progress of chronic diseases related to inflammation such as diabetes, obesity,
\nneurodegeneration, cancers, and cardiovascular diseases, among other conditions.
\nKeywords: polyphenols; immune system; inflammation; molecular mechanisms; nuclear factor
\nkappa-light-chain-enhancer of activated B cells (NF-\u03baB); arachidonic acid; mitogen-activated
\nprotein Kinase (MAPK); cytokines; oxidative stress; reactive oxygen species (ROS); cyclooxygenase
\n(COX); nitric oxide synthase (NOS); lipoxygenase (LOX); superoxide dismutase (SOD); inhibitor
\nof kappa kinase (IKK); extra-cellular signal regulated kinases (ERK); cancer; anti-inflammation;
\nanti-tumorigenic; chronic inflammatory conditions; macrophages; T helper 1 (Th1); Th17; Treg<\/p>\n