Effects of Flavonoids and other Polyphenols on Inflammation

Abstract

Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others.

Keywords:

• asthma
• inflammatory bowel disease
• arthritis
• pharmacokinetics
• atherosclerosis
• mechanism of action

ACKNOWLEDGEMENTS

This study was supported by grants of the Ministry of Science and Innovation (AGL2008-04332 and SAF2008-01432) and the CIBERehd. RG is funded by the CIBERehd. RLP and IB are funded by the Ministry of Science and Innovation. The CIBERehd is funded by the Instituto de Salud Carlos III. The group is member of the Network for Cooperative Research on Membrane Transport Proteins (REIT), co-funded by the Ministry of Education and Science, Spain and the European Regional Development Fund (Grant (BFU2007-30688-E/BFI). The authors also acknowledge the support of the Fundación Ramón Areces.