The Role of Quercetin, Flavonols and Flavones in Modulating Inflammatory Cell Function

Abstract

Flavonoids are polyphenolic substances derived from plants that play several pharmacological activities. They possess anti-viral, anti-microbial, anti-inflammatory and anti-allergic potential that can be expressed on different cell types, both in animal and human models. Many of these properties prove inhibitory to a huge panoply of molecular targets in the micromolar concentration range, either by down-regulating or suppressing many inflammatory pathways and functions. Flavonoids exert their properties both as purified aglycone molecules and as plant extracts. Depending on little changes in the flavone-backbone and on subtle mechanisms of cell behavior and responsiveness, flavonoids can play a modulating, biphasic and regulatory action on immunity and inflammation; in this context only few flavones and flavonols have been assayed, mainly because of their chemical similarity with quercetin, so evidence reported in the literature about the action of flavonoids is limited to a restricted group of molecules. Many of the effects reported about flavonoids regard quercetin, as probably the most diffused and known nature-derived flavonol. Quercetin has shown a biphasic behavior in basophils at nanomolar doses and hence its action on cells involved in allergic inflammation is here described. Like many other molecules sharing a flavone ring, quercetin affects immunity and inflammation by acting mainly on leukocytes and targeting many intracellular signaling kinases and phosphatases, enzymes and membrane proteins often crucial for a cellular specific function. This overview collects and discusses the role of flavonoids as antiinfectious and anti-inflammatory compounds, trying to focus on the complex and modulating interaction of these polyphenolic substances with cell function. However, the wide group of intracellular targets and the elevated number of natural compounds potentially effective as anti-inflammatory therapeutical agents, asks for further insights and evidence to comprehend the role of these substances in animal cell biology. Keywords: Aryl hydrocarbon receptors, basophils, biphasic modulation, flavonoids, inflammation, quercetin, anti-allergic, aglycone, flavonol, kaempherol, anthocyanidins, ubiquitous, isorhamnetin, glucosidase, glucuronic acid, luteolin, apigenin, Barleria prionitis, A. berlandieri, A. greggi, R. cotinus, Scutellaria baicalensis Georgi, human umbilical vein endothelial cells (HUVEC), protein kinase C (PKC), Kaempherol glycosides, lysozime, Helicobacter pylori, rat basophilic leukaemia cell line (RBL-2H3), Cistus laurifolius, Oxytropis falcata, β-exosaminidase, synergistic mechanism, Myricetin, ovoalbumin (OVA), tumor necrosis factor-alpha (TNF-α), human embryonic kidney cell culture (HEK293), rheumatoid arthritis (RA), fibroblast-like synovial cells (FLS), extracellular signal regulated kinase (ERK), lipopolysaccharide (LPS), peripheral blood mononuclear cells (PBMC), cytometry, glial fibrillary acidic protein (GFAP), ceruloplasmin (CP), pathogen associated molecular pattern molecule (PAMP), high mobility group box 1 protein (HMGB1), factor-kappa B, activator protein-1, extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), IB kinase (IKK), nuclear factor-kappaB (NFB), hydrocarbon receptor (AhR), basic helix-loop-helix (bHLH), Per-Arnt-Sim (PAS), Polychlorinated biphenyls (PCBs), aryl hydrocarbon receptor (AHR), Listeria monocytogenes, anaphylactic reactions, lysophospholipase, concanavalin A (ConA), phorbol esters (PMA), formylated peptides (fMLP), Tanacetum parthenium, mucosal mast cells (MMC), rat mast cell protease, heterotrimeric G protein, calcium ionophores