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Quercetin-Bromelain supplies the flavonoid quercetin extracted from seed pods of the Dimorphandra mollis plant. Flavonoids are "semi-essential" nutrients found in many plants and foods. Bromelain is an enzyme complex derived from the pineapple stem.
Quercetin modifies the body's response to antigenic substances, inhibits formation of free radicals and supports circulatory health by promoting integrity of tissues in small blood vessels. Bromelain supports tissue comfort and may enhance quercetin absorption.
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.
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
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
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.*
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.
1.Nishino, H., et. al., “Quercetin interacts with calmodulin, a calcium regulatory protein.” Experientia 1984;40:184-5.
2.Busse, W.W., Kopp, D.E., Middleton, E., “Flavonoid modulation of human neutrophil function.” J. Allergy Clin. Immunol. 1984;73:801-9.
3.Havsteen, B,. “Flavonoids, a class of natural products of high pharmacological potency.” Biochemical Pharmacology 1983;32(7):1141-48.
4.Middleton, E., “The Flavonoids.” Trends in Pharmaceutical Sciences 1984;5:335-8.
5.Otsuka, H. et. al., “Histochemical and functional characteristics of metachromatic cells in the nasal epithelium in allergic rhinitis: Studies of nasal scrapings and their dispersed cells.” J. Allergy Clin. Immunol.1995;96:528-36.
6.Fox, C.C., et. al., “Comparison of human lung and intestinal mast cells.” J. Allergy and Clin. Immunol. 1988;81:89-94.
7.Pearce, F.L., Befus, A.D., Bienenstock, J., “Mucosal mast cells III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells.” J. Allergy and Clin. Immunol. 1984;73:819-23.
8.Middleton, E. Drzewiecki, G., Krishnarao, D., “Quercetin: an inhibitor of antigen-induced human basophil histamine release.” J. of Immunology 1981;127(2):546-50.
9.Bennett, J.P., Gomperts, B.D., Wollenweber, E.,“ Inhibitory effects of natural flavonoids on secretion from mast cell and neutrophils.” Arzneim. Forsch/Drug Res. 1981;31(3):433-7.
10.Middleton, E. Drzewiecki G., “Naturally occurring flavonoids and human basophil histamine release.” Int. Archs Allergy appl. Immun. 1985;77:155-7.
11.Yoshimoto, T. et. al., “Flavonoids: potent inhibitors of arachidonate 5-lipoxygenase.” Biochemical and Biophysical Research Communications 1983;116(2):612-18.
12.Della Loggia, R., et. al., “Anti-inflammatory activity of benzopyrones that are inhibitors of cyclo- and lipo-oxygenase.” Pharmacological Research Communications 1988; 20(Supp. V):91-94.
13.Middleton, E., Suresh, A., “Quercetin inhibits lipopolysaccharide-induced expression of endothelial cell intracellular adhesion molecule-1.” Int. Arch. Allergy Immunol. 1995;107:435-6.
14.Taussig, S.J., Batkin, S., “Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application.” An Update Journal of Ethnopharmacology 1988;22:191-203.
15.Lotz-Winter, H., “On the pharmacology of bromelain: An update with special regard to animal studies on dose-dependent effects.” Planta Medica 1990;56:249-53.
16.Taussig, S.J., “The mechanism of the physiological action of bromelain” Medical Hypothesis 1980;6:99-104.
17.Ako, H. Cheung, A.H.S., Matsuura, P.K., “Isolation of a fibrinolysis activator from commercial bromelain.” Arch. Int. Pharmacodyn. 1981;284:157-67.
18.Afanas’ev, I.B. et. al., “Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation.” Biochemical Pharmacology 1989;38(11):1763-69.
19.De Whalley, C.V., “Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages.” Biochemical Pharmacology 39(11):1743-50.
20.Beretz, A. Stierle, A., Anton, R. Cazenave, J., “Role of cyclic AMP in the inhibition of human platelet aggregation by quercetin, a flavonoid that potentiates the effect of prostacyclin.” Biochemical Pharmacology 1981;31(22):3597-600.
21.Heinicke, R. van der Wal, L. Yokoyama, M., “Effect of bromelain (Ananase®) on human platelet aggregation. ”Experientia 1972;28(7):844.
22.Hollma, P. et. al., “Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers.” Am. J. Clin. Nutr. 1995;62:1276-82.
23.Giller, F.B., “The effects of bromelain on levels of penicillin in the cerebrospinal fluid of rabbits.” A., J. Pharm. 1962;134:238-244.
24.Bodi, T., “The effect of oral bromelain on tissue permeability to antibiotics and pain response to bradykinin; double-blind studies on human subjects.” Clin. Med. 1965;72:61-65.
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