Table 2.

In vitro anti-inflammatory activity of quercetin, curcumin and resveratrol: concerns and suggestions for a proper study of these poor available polyphenols.

Polyphenol	Studied Effects	Models	Findings	Main Concerns	Possible Suggestions
Quercetin	Pro-inflammatory cytokines release inhibition Cyclooxygenase and lipoxygenase inhibition Inhibition of Src- and Syk-mediated PI3K-(p85) Inhibition of intracellular calcium influx and PKC signaling	Human umbilical cord blood-derived cultured mast cells (hCBMCs) Human normal peripheral blood mononuclear cells (PBMC) Human monocytes (THP-1) RAW 264.7 macrophages T lymphocytes Mast cells Microglial cells BV-2	Anti-inflammatory activity only exerted at concentrations >1 μM, more often in the range 10–100 μM [73,75]	Effective concentrations are high if compared with those normally achievable in vivo [73] Quercetin is considered one of the most impacting dietary flavonoids, but it mostly occurs in food as glycoside [23] In vitro demonstrated effects could only be referred to repeated administration of high dosesof quercetin [76,77]	Quercetin should be tested in vitro at nanomolar level Quercetin should be investigated both as single compound and in matrix when its dietary role is taken into account Investigation on quercetin should consider simulated digestion in order to evaluate the role of metabolites
Curcumin	Upstream signaling and modulation of transduction and transcription factors Downstream level of pro-inflammaotry markers	Different human immune cell lines Human umbilical vein endothelial cells (HUVEC) Tracheal smooth muscle cells Head and neck cancer cells RAW 264.7 macrophages Oesophageal epithelial cells Microglial cells	Strong anti-inflammatory activity exerted at concentrations >10 μM [73,92]	Effective concentrations are high if compared with those normally achievable in vivoand in vitro tests hardly could explain clinical findings [73] Curcumin occurs in food and food supplements in complex with other curcuminoids [23]	Curcumin and curcuminoids should be tested in vitroat nanomolar level Curcumin should be investigated both as single compound and in matrix together with other curcuminoids
Resveratrol	Arachidonic acid pathways MAPKs pathways NF-κB signaling AP-1 pathways Pro-inflammatory cytokines release inhibition	A549 adenocarcinomic human alveolar basal epithelial cells Human keratinocytes Human mammary epithelial cells Human T lymphocytes THP-1 HUVEC RAW 264.7 macrophages Myeloid leukemia cells Cardiomyocytes Chondrocytes Mesangial cells Osteoblasts Pancreatic cancer cells Benign prostatic hyperplasia epithelial cell line (BPH-1)	Anti-inflammatory activityexerted at concentrations >1 μM [73,93]	Effective concentrations are high if compared with those normally achievable in vivoand in vitro tests hardly could explain clinical findings [73] In vitro effects could be not referred to dietary resveratrol contained in grape, wine or in other source, given its poor content [37,93]	Resveratrol should be tested in vitro at nanomolar level Investigation on resveratrol should consider simulated digestion in order to evaluate the role of metabolites