Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans

Abstract

Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell “stabilizer”, is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD2. Que and cromolyn also inhibit histamine, leukotrienes and PGD2 from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption.

Quercetin But Not Quercitrin Ameliorates Tumor Necrosis Factor-Alpha-Induced Insulin Resistance in C2C12 Skeletal Muscle Cells

“…[40][41][42] However, it has also been reported that dietary quercetin did not reduce NF-κB expression/activation in the renal cortex of rats, 43) which suggests that flavonoids may act in an organspecific manner. A more thorough understanding of the effects of dietary quercetin will require further investigation.…”

Targeting IL-33 in Autoimmunity and Inflammation

“…They both inhibit the release of histamine, leukotrienes, and prostaglandin D 2 from human cultured MCs in response to cross-linkage of Fc«RI (Kimata et al, 2000). Quercetin also inhibits histamine, IL-6, IL-8, TNF-a, and tryptase release from human MCs Park et al, 2008), as well as asthma in a guinea pig model (Moon et al, 2008) and contact dermatitis in humans (Weng et al, 2012). Luteolin has also been reported to inhibit stimulation of activated T cells (Kempuraj et al, 2008), keratinocytes (Weng et al, 2014a), and microglia (Jang et al, 2008).…”

About High Potent Efficacy of FLEBIL in Pharmacotherapy of Hemorrhoidal Disease Associated with Irritable Bowel Syndrome (IBS)

“…It has been identified potent mast cells stabilizer effect of natural components (flavonoids, phenols, terpenoids, coumarins) [4,5]. Furthermore considerable non-gastrointestinal symptoms are typical for IBS as well.…”

“…Particularly, flavonoids express mast cells stabilizer effect, exactly among them are quercetin, rutin, fisetin, kaempferol. Furthermore quercetin decreases IL-1b, IL-6, IL-8 and TNF production and more effectively inhibits cytokines release from human mast cells, than mast cells well known stabilizer cromolyn [4][5][6][7].…”