Activities of flavonoids

CUSHMAN M, NAGARATHMAN D, BURG D L and GEAHLEN R L (1991) Synthesis and protein-tyrosine kinase inhibitory activity of flavonoids analogues Journal cjf Medicinal Chemistry 34, 798-806. 

Flavonoids in general are extensively metabolized by enterocyte and hepatic cell enzymes and by intestinal microflora. Therefore, it is necessary to explore the biological activity of flavonoids and their metabolites in specific tissues, because the metabolites found in the blood flow or any specific organ may differ among themselves and from... 

Other Examples of Protective Activity of Flavonoids Against Free Radical-Mediated Damage in Biological Systems... 

Antioxidant activity of flavonoids has already been shown about 40 years ago [90,91]. (Early data on antioxidant flavonoid activity are cited in Ref. [92].) Flavonoids are polyphenols, and therefore, their antioxidant activity depends on the reactivity of hydroxyl substituents in hydrogen atom abstraction reactions. As in the case of vitamins E and C, the most studied (and most important) reactions are the reactions with peroxyl radicals [14], hydroxyl radicals [15], and superoxide [16]. 

The ability of flavonoids (quercetin and rutin) to react with superoxide has been shown in both aqueous and aprotic media [59,94]. Then, the inhibitory activity of flavonoids in various enzymatic and nonenzymatic superoxide-producing systems has been studied. It was found that flavonoids may inhibit superoxide production by xanthine oxidase by both the scavenging of superoxide and the inhibition of enzyme activity, with the ratio of these two mechanisms depending on the structures of flavonoids (Table 29.4). As seen from Table 29.4, the data obtained by different authors may significantly differ. For example, in recent work [107] it was found that rutin was ineffective in the inhibition of xanthine oxidase that contradicts the previous results [108,109], The origins of such big differences are unknown. 

The application of flavonoids for the treatment of various diseases associated with free radical overproduction is considered in Chapter 29. However, it seems useful to discuss here some studies describing the activity of flavonoids under certain pathophysiological conditions. Oral pretreatment with rutin of rats, in which gastric lesions were induced by the administration of 100% ethanol, resulted in the reduction of the area of gastric lesions [157]. Rutin was found to be an effective inhibitor of TBAR products in the gastric mucosa induced by 50%i ethanol [158]. Rutin and quercetin were active in the reduction of azoxymethanol-induced colonic neoplasma and focal area of dysplasia in the mice [159], Chemopreventive effects of quercetin and rutin were also shown in normal and azoxymethane-treated mouse colon [160]. Flavonoids exhibited radioprotective effect on 7-ray irradiated mice [161], which was correlated with their antioxidative activity. Dietary flavones and flavonols protected against the toxicity of the environmental contaminant dioxin [162], Rutin inhibited ovariectomy-induced osteopenia in rats [163],... 

The competition between antioxidant and prooxidant activity of flavonoids depends firstly on their chemical structure. If we suppose that the oxidation of flavonoids (Reaction (17)) takes place by one-electron transfer mechanism, then it must depend on the capacity of flavonoids to donate an electron, i.e., on their one-electron oxidation potentials. 

Although no good quantitative correlation between redox potentials of flavonoids and their prooxidant activities still was not documented, a relationship between the prooxidant toxicity of flavonoids to HL-60 cells and redox potentials apparently takes place [176]. However, there is a simple characteristic of possible prooxidant activity of flavonoids, which increases with an increase in reactive hydroxyl groups in the B ring. From this point of view, the prooxidant activity of flavonoids should increase in the range kaempferol < quercetin < myricetin (Figure 29.7). Thus, for many flavonoids the ratio of their antioxidant and prooxidant activities must depend on the competition between Reactions (14) and (15) and Reaction (17). 

At present, many natural and synthetic chelators have been studied as potential pharmacological agents for the treatment of iron or copper overload under various pathophysiological conditions. (The chelating activity of flavonoids was already discussed above and the application of chelators in thalassemia and some other pathologies is considered in Chapter 31.) There are specific thermodynamic demands to chelators to be efficient antioxidants [369], We will consider just several chelators of potential therapeutic importance. 

Sanders et al. [133] found that although quercetin treatment of streptozotocin diabetic rats diminished oxidized glutathione in brain and hepatic glutathione peroxidase activity, this flavonoid enhanced hepatic lipid peroxidation, decreased hepatic glutathione level, and increased renal and cardiac glutathione peroxidase activity. In authors opinion the partial prooxidant effect of quercetin questions the efficacy of quercetin therapy in diabetic patients. (Antioxidant and prooxidant activities of flavonoids are discussed in Chapter 29.) Administration of endothelin antagonist J-104132 to streptozotocin-induced diabetic rats inhibited the enhanced endothelin-1-stimulated superoxide production [134]. Interleukin-10 preserved endothelium-dependent vasorelaxation in streptozotocin-induced diabetic mice probably by reducing superoxide production by xanthine oxidase [135]. 

It has been established that the free radical scavenger activity of flavonoids is responsible for the antioxidant effect [95,96], The beneficial antitumour effect of quercetin has also been demonstrated [97,98],... 

The purpose of this review is to discuss recent developments related to the chemistry and medicinal properties of natural flavonoids. This review covers more recent reports (2005 to the present date) of antimicrobial activity of flavonoids (antibacterial and antifungal), as well as the antiviral activity of these compounds. 

Habbu PV, Mahadevan KM, Shastry RA, Manjunatha H. (2009) Antimicrobial activity of flavonoid sulphates and other fractions of Argyreia speciosa (Burm. f.) Boj. Indian J Exp Biol 47 121-128. 

Hukeri GA, Kalyani HK. (1988) Hypoglycemic activity of flavonoids of Phyllanthus frametus in rats. Fitoterapia 59 68-70. 

The biological activity of flavonoids has attracted much interest in the part twenty years and a few compounds of this class have been shown to have AChEI effects. The flavanone naringenin (74) from Citrus junos (Rutaceae) ameliorated scopolamine-induced amnesia in mice, which may be related to an antiAChE effect, since naringenin was shown to inhibit AChE in vitro dose dependently. A recent theoretical study has shown that flavonoids and xanthones exhibit polyvalent effects such as antioxidant, amyloid reduction and cholinesterase inhibition, which made them interesting candidates for further studies. 

Miyake, Y. et al., Isolation of C-glucosylflavone from lemon peel and antioxidative activity of flavonoid compounds in lemon fruit, J. Agric. Food Ghem., 45, 4619, 1997. 

Jaakola, L. et al.. Activation of flavonoid biosynthesis by solar radiation in bilberry (Vaccinium myrtillus L.) leaves, Planta, 218, 721, 2004. 

Karton, Y. et al.. Synthesis and biological activities of flavonoid derivatives as adenosine receptor antagonists, J. Med. Chem., 39, 2293, 1996. 

Rios, J.L. et al., Antioxidant activity of flavonoids from Sideritis javalambrensis, Phytochemistry, 31, 1947, 1992. 

Trakoontivakom, G. et al., Stmctural analysis of a novel antimutagenic compound, 4-hydroxy-panduratin A, and the antimutagenic activity of flavonoids in a Thai spice, fmgerroot (Boesenber-... 

Shahat, A. A., S.I. Ismail, F. N. Hammouda, and S.A. Azzam. 1998. Anti-HIV activity of flavonoids and proanthocyanidins from Crataegus sinalica. Phytomedicine 5 133-136. 

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