Procyanidins and inflammation: molecular targets and health implications.

The inflammatory response has been implicated in the pathogenesis of many chronic diseases. Thus, the modulation of the inflammatory response by the consumption of bioactive food compounds, such as procyanidins, is a powerful tool to promote health. Procyanidin-mediated anti-inflammatory molecular mechanisms include, among others, the modulation of the arachidonic acid pathway, the inhibition of the gene transcription, protein expression and enzymatic activity of eicosanoid generating enzymes, the production and secretion of inflammatory mediators (such as cytokines and nitric oxide), the inhibition of mitogen-activated protein kinase (MAPK) pathway activation, and the modulation of the nuclear factor-κB (NF-κB) pathway. The NF-κB pathway can be regulated by procyanidins at several levels. During early events in NF-κB signaling, procyanidins modulate Iκκ activity, and the cytoplasmic retention of p65:p50 NF-κB by the inhibition of IκB phosphorylation and proteasomal degradation, while at late stages, they affect the nuclear translocation of pro/anti-inflammatory NF-κB homo/hetero dimers and their subsequent binding to the promoter regions of target genes. To identify and understand the value of procyanidins in the modulation of the inflammatory response, the molecular mechanisms underlying the anti-inflammatory activities and prohomeostatic effects of procyanidins need to be investigated further.