Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

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Secretory products of macrophages.

The effects of dietary fish-oil fatty acids on the function of the 5-lipoxygenase pathway of peripheral-blood polymorphonuclear leukocytes and monocytes were determined in seven normal subjects who supplemented their usual diet for six weeks with daily doses of triglycerides containing 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid. The diet increased the eicosapentaenoic acid content in neutrophils and monocytes more than sevenfold, without changing the quantities of arachidonic acid and docosahexaenoic acid. When the neutrophils were activated, the release of [3H]arachidonic acid and its labeled metabolites was reduced by a mean of 37 per cent, and the maximum generation of three products of the 5-lipoxygenase pathway was reduced by more than 48 per cent. The ionophore-induced release of [3H]arachidonic acid and its labeled metabolites from monocytes in monolayers was reduced by a mean of 39 per cent, and the generation of leukotriene B4 by 58 per cent. The adherence of neutrophils to bovine endothelial-cell monolayers pretreated with leukotriene B4 was inhibited completely, and their average chemotactic response to leukotriene B4 was inhibited by 70 per cent, as compared with values determined before the diet was begun and six weeks after its discontinuation. We conclude that diets enriched with fish-oil-derived fatty acids may have antiinflammatory effects by inhibiting the 5-lipoxygenase pathway in neutrophils and monocytes and inhibiting the leukotriene B4-mediated functions of neutrophils.

Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function

THE slow-reacting substance of anaphylaxis was recognized as a discrete biologic entity 1 , 2 three to four decades before it was chemically defined as three specific cysteinyl leukotriene products of the 5-lipoxygenase pathway.3 4 5 6 7 In the interim, it was hypothesized that this moiety might function as a proinflammatory mediator of bronchoconstriction and vasopermeability in diseases of immediate hypersensitivity.8 9 10 11 Since the chemical characterization of the slow-reacting substance of anaphylaxis as several cysteinyl leukotrienes and the identification and biochemical assessment of the enzymes in the 5-lipoxygenase pathway (Fig. 1 and Glossary), the products of this pathway have been implicated in a much broader variety of functions . . .

Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases.

Publisher Summary This chapter reviews information on eosinophil structure and function and provide evidence for the eosinophil as an effector cell for killing helrninths and for causing tissue damage in hypersensitivity diseases. The mammalian eosinophil is distinguished by its characteristic granules. The chapter describes specific or secondary granules with an electron-dense core and an electron-radiolucent matrix and two other distinctive types of eosinophil granules as well. While granules with crystalloid cores are characteristic of most mammalian eosinophils—the horse eosinophil is a notable exception—cores have not been observed in lowest vertebrates with the exception of certain teleost fishes and some birds. The evidence reviewed in the chapter indicates that the eosinophil has the ability to kill many species of helminths and likely does so during worm infection. This toxic ability appears to be regulated by several other cells including mast cells, monocytes, and T lymphocytes. It has also been found that an eosinophil-related protein appears to play an undefined role in human reproduction.

The Eosinophilic Leukocyte: Structure and Function

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R A Lewis

Papers

The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology.