Flavonoids action

Peer WA, Murphy AS. 2006. Flavonoids as signal molecules Targets of flavonoid action. In Grotewold E, Eds. The Science of Flavonoids. New York Springer., pp. 239-268. 

In addition to variations in citrus extracts, there are features of bioflavonoid effects on the mammalian body which may have contributed greatly to the controversy concerning flavonoid action. In 1940 Yosida (13) and in 1955 Rinehart (14) reported effects of hesperidin on rheumatic fever. Yosida determined the erythrocyte sedimentation rate (ESR) before and after injecting hesperidin into patients. In 26 sets of determinations the ESR was retarded in 19, unchanged in 3 and accelerated in 4 cases. Rinehart administered hesperidin to 26 patients, 22 showed a decreased ESR, 1 an unchanged and 3 an increased ESR. Hence, by the usual interpretation that an increased ESR indicates pathology, hesperidin in some cases showed beneficial effects, in others no effect and in still others made the disease worse. 

A theory of flavonoid action as described above appears to explain several confusing features of their action, i.e., the wide variety of effects in the animal body, why a considerable number of flavonoids show activity, the trimodal action and the apparent inconsistent effects. 

The controversies have long hampered efforts to make effective use of bioflavonoids in nutrition and medicine, but research of recent years has shed considerable light on phenomena underlying inconsistent flavonoid action. Findings in the following areas have made substantial contributions to understanding bioflavonoid action ... 

Bioflavonoids have been discovered to exert an antiadhesive action on blood cells. Erythrocyte adhesion is a general accompaniment of disease and trauma and has rheological implications. Hesperidin or other of the less active fiavonoids administered to a series of patients or added to blood in vitro may show three kinds of activity, inhibit blood cell adhesion in some, no effect in others or accelerate adhesion in still others, i.e., a trimodal action. This characteristic feature of flavonoid action undoubtedly has been interpreted as an inconsistent effect. However, all fiavonoids do not show a trimodal action. Also, there is considerable evidence linking rheological effects of bioflavonoids to their effects on capillary defects and beneficial effects in disease. Thus, the trimodal effects may explain the apparent inconsistent action against the above phenomena. 

The mechanism of action proposed is based on a direct binding to the channel and the following partial block of the ATP-binding pocket of CFTR (French et al., 1997), a mechanism similar to that used by genistein to inhibit the activity of other ATP-utilizing enzymes such as protein kinases and topoisomerase II (Polkowski and Mazurek, 2000 and refs therein). The selection of flavonoid compounds or the development of synthetic drugs reasonably selective for CFTR activation might be an area for future clinical trials. 

Cyanidin is the most common anthocyanin in foods. In addition, anthocyanins are stabilized by the formation of complexes with other flavonoids (co-pigmentation). In the United States, the daily anthocyanin consumption is estimated at about 200 mg. Several promising studies have reported that consumption of anthocyanin-rich foods is associated with reductions of the risks of cancers - and atherosclerosis and with preventive effects against age-related neuronal and behavioral declines. These beneficial effects of anthocyanins might be related to their reported biological actions such as modulators of immune response and as antioxidants. Knowledge of anthocyanin bioavailability and metabolism is thus essential to better understand their positive health effects. 

Carmen Socaciu was bom in Cluj-Napoca, Romania and earned a BSc in chemistry in 1976, an MSc in 1977, and a PhD in 1986 from the University Babes-Bolyai in Cluj-Napoca, an important academic centre located in the Transylvania region. Dr. Socaciu worked as a researcher in medical and cellular biochemistry for more than 10 years, and became a lecturer in 1990 and full professor in 1998 in the Department of Chemistry and Biochemistry of the University of Agricultural Sciences and Veterinary Medicine (USAMV) in Cluj-Napoca. She extended her academic background in pure chemistry (synthesis and instrumental analysis) to the life sciences (agrifood chemistry and cellular biochemistry). Her fields of competence are directed especially toward natural bioactive phytochemicals (carotenoids, phenolics, flavonoids), looking to advanced methods of extraction and analysis and to their in vitro actions on cellular metabolism, their effects as functional food ingredients, and their impacts on health. 

Allelopathic inhibition of mineral uptake results from alteration of cellular membrane functions in plant roots. Evidence that allelochemicals alter mineral absorption comes from studies showing changes in mineral concentration in plants that were grown in association with other plants, with debris from other plants, with leachates from other plants, or with specific allelochemicals. More conclusive experiments have shown that specific allelochemicals (phenolic acids and flavonoids) inhibit mineral absorption by excised plant roots. The physiological mechanism of action of these allelochemicals involves the disruption of normal membrane functions in plant cells. These allelochemicals can depolarize the electrical potential difference across membranes, a primary driving force for active absorption of mineral ions. Allelochemicals can also decrease the ATP content of cells by inhibiting electron transport and oxidative phosphorylation, which are two functions of mitochondrial membranes. In addition, allelochemicals can alter the permeability of membranes to mineral ions. Thus, lipophilic allelochemicals can alter mineral absorption by several mechanisms as the chemicals partition into or move through cellular membranes. Which mechanism predominates may depend upon the particular allelochemical, its concentration, and environmental conditions (especially pH). 

Viruses don t have a reproductive system of their own and need to take over healthy cells by puncturing them with tiny spikes called hemagglutinin so that they can use the cells reproductive mechanism to make more viruses. These viral spikes are coated with an enzyme called neuraminidase, which helps to break down cellular walls. Flavonoids that occur in elderberries inhibit viral action and thereby improve immune response. It is thought that the flavoniods may also inhibit the action of neuraminidase. 

Naturally occurring compounds such as phytochemicals, which possess anticar-cinogenic and other beneficial properties, are referred to as chemopreventers. One of the predominant mechanisms of their protective action is due to their antioxidant activity and the capacity to scavenge free radicals. Among the most investigated chemopreventers are some vitamins, plant polyphenols, and pigments such as carotenoids, chlorophylls, flavonoids, and betalains. Resolution of the potential protective roles of... 

Some of the bioactive phytochemicals found in fmits and vegetables are polyphenols, including flavonoids. This chapter provides a general overview of the relationship between flavonoids and health. The mechanisms of action believed to be behind the healthful effects of some compounds will also be mentioned. 

Phytochemicals or phytonutrients are bioactive substances that can be found in foods derived from plants and are not essential for life the human body is not able to produce them. Recently, some of their characteristics, mainly their antioxidant capacity, have given rise to research related to their protective properties on health and the mechanisms of action involved. Flavonoids are a diverse group of phenolic phytochemicals (Fig. 6.1) that are natural pigments. One function of flavonoids is to protect plants from oxidative stress, such as ultraviolet rays, environmental pollution, and chemical substances. Other relevant biological roles of these pigments are discussed in other chapters of this book. 

There are several mechanisms involved in the vasodilator effect of flavonoids. The main mechanism seems to be related to the inhibition of protein kinase C or some of the processes activated by this protein. The inhibition of other protein kinases and cyclic nucleotide phosphodiesterase activity and blockage of calcium entry can also contribute to this effect to a greater or lesser extent (Alvarez Castro and Orallo, 2003 Herrera and others 1996). Certain flavonoids, like the flavonol myricetin, have a two-phase action on blood vessels vasoconstrictor in lowest active concentrations and vasodilator in higher concentrations (Alvarez Castro and Orallo, 2003). 

Alvarez Castro E and, Orallo Cambeiro F. 2003. Actividad biologica de los flavonoides (II). Action cardiovascular y sanguinea. OFFARM 22 102-110. 

Cazarolli LH, Zanatta L, Alberton EH, Figueredo MS, Folador P, Damazio RG, Pizzolatti MG and Silva FR. 2008. Flavonoids cellular and molecular mechanisms of action in glucose homeostasis. Mini Rev Med Chem 8(10) 1032-1038. 

Nijveldt RJ, vanNood E, van Hoorn DE, Boelens PG, vanNorrenK and van Leeuwen PA. 2001. Flavonoids a review of probable mechanisms of action and potential applications. Am J Chn Nutr 74(4) 418-425. 

People in France eat a lot of fatty foods but suffer less from fatal heart strokes than people in the northern regions of Europe or in North America, where wine is not consumed on a regular basis ( French paradox ). There is an increased favorable effect from red wine. The unique cardioprotective properties of red wine are due to the action of flavonoids, which are minimal in white wine. The best-researched flavonoids are resveratrol and quercetin, which confer antioxidant properties more potent than a-tocopherol. 

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