Down-regulates the Body’s Response to Environmental Challenges
Quercetin is a member of the flavonoid family, a diverse group of low molecular-weight compounds found throughout the plant kingdom. Flavonoids exhibit numerous biological activities, many of which are directly beneficial to human health. Quercetin, which belongs to the “flavonol” subgroup, is one of the most versatile and important flavonoids.
Quercetin has a broad range of activity, much of which stems from its interaction with calmodulin, a calcium-regulatory protein.1 Calmodulin transports calcium ions across cellular membranes, initiating numerous cellular processes. Quercetin appears to act as a calmodulin antagonist.1 Through this mechanism, quercetin functions at the cell-membrane level with a membrane-stabilizing action.2 Quercetin inhibits calmodulin-dependent enzymes present at cell membranes such as ATPases and phospholipase, thereby influencing membrane permeability.3 Quercetin affects other calmodulin-dependent enzymes that control various cellular functions, including the secretion of histamine from mast cells.4 A number of investigations have corroborated quercetin’s ability to reduce histamine secretion from mast cells in various tissues, and also from basophils.5,6,7,8,9,10
Quercetin modifies the body’s response to antigenic substances.* Suppression of histamine secretion from mast cells is one of quercetin’s most clinically important effects. Quercetin acts on ATPase at the membranes of histamine-containing granules in mast cells.3 Mast-cell degranulation and subsequent release of histamine into the bloodstream is an integral part of the body’s response to environmental challenges.
Maintains Tissue Comfort by Regulating Enzymes*
Quercetin’s enzyme-inhibiting action extends to enzymes such as phospholipase, which catalyzes the release of arachidonic acid from phospholipids stored in cell membranes.4,10 Arachidonic acid serves as the key substrate for substances such as thromboxanes, inflammatory prostaglandins and leukotrienes. In addition, quercetin inhibits the enzymes cyclooxygenase and lipoxygenase, which catalyze the conversion of arachidonic acid into its metabolites.4,10,11,12 Reducing levels of these metabolites, as well as histamine levels, is beneficial in maintaining the normal comfort level of body tissues and structures.
Quercetin has also been shown to limit the function of adhesion molecules on endothelial cells.13 Adhesion molecules are involved in physiologic processes that influence tissue comfort.13
Bromelain is a complex substance derived from the pineapple stem largely composed of proteolytic (protein-digesting) enzymes. Bromelain acts by a variety of mechanisms to help maintain tissues in a normal state of comfort.14,15 Several investigators, including Taussig16 and Ako, et. al.,17 have presented evidence that bromelain is a fibrinolytic agent, i.e., it induces the breakdown of fibrin, a plasma protein that blocks tissue drainage. The generally accepted mechanisms involve direct proteolysis of fibrin by bromelain and activation of plasmin, a serum protease.16 Plasmin acts on fibrinogen (the precursor to fibrin), forming peptides which stimulate PGE1, a prostaglandin that helps maintain tissue comfort.16
Helps Maintain Health of Blood Vessels by Modifying Oxidation of LDL Cholesterol* — Quercetin’s Antioxidant Action
Quercetin is a versatile and effective antioxidant that scavenges a variety of free-radicals such as hydroxyl and lipid peroxy radicals.18 Quercetin also chelates ions of transition metals such as iron, which can initiate formation of oxygen free radicals.18 LDL cholesterol is vulnerable to oxidation by lipid peroxides. Oxidized LDL is absorbed by macrophages and arterial endothelial cells, leading to the formation of “foam cells,” and eventually plaque deposits, in arterial walls. Quercetin has been shown to protect LDL from oxidation, both by lipid peroxides and transition metal ions.19
Helps Maintain Normal Blood Viscosity*
Quercetin inhibits blood platelet aggregation (clumping), by potentiating PGI2, an anti-aggregatory prostaglandin, and by raising platelet cyclic AMP levels.20 Human studies have revealed that bromelain also reduces platelet aggregation.21 These properties qualify both quercetin and bromelain as valuable dietary ingredients for maintaining cardiovascular health.*
Bromelain May Enhance Quercetin Absorption
In addition to the actions described above that support the effects of quercetin, bromelain may also assist the absorption of quercetin in the G.I. tract. (Quercetin is generally believed to be poorly absorbed, although a recent study by Hollman et. al.,22 which concluded that humans do in fact absorb appreciable amounts of quercetin, contradicts this assumption.) Studies have shown that bromelain enhances absorption of antibiotics, presumably by increasing permeability of the gut wall.23, 24 Given that quercetin is a low molecular-weight compound, it is plausible that simultaneously ingested bromelain likewise enhances quercetin absorption.
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