Flavones, inhibitor effect

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],... 

Flavone has been shown to be effective at 170 /iM concentration to inhibit HDAC-1 activity, and also to induce histone H3 acetylation in NB4 APL cell lines. Flavone s mechanism of HDAC inhibition is currently unknown, but it has been proposed that similar to the inhibitors of kinases, it might occupy the exit channel or an alternative, shallow binding site found in HDAC with possible effects of causing allosteric modulation. This blockage or allosteric modulation would promote inhibition. ... 

Flavonoids are well known as inhibitors of hyaluronidase. Li 1950 Rodney et al, reported the effect of several flavonoids on hyaluronidase using in vitro and in vivo methods [79], Knppusamy et al. investigated the structure-activity relationship of die flavonoids as inhibitors of testicular hyaluronidase [80] and hyaluronidase from snake, scorpion, and bee venom [81]. They showed that flavones. flavanols. and chalcones possess the general ability to inhibit hyaluronidase Kinetic investigations showed that these compounds acted as competitive inhibitors [80]. Several hyaluronidase inhibitors were shown to be able to delay the action of snake venom when injected into mice [8ll One caimnt rule out the possible interaction of the flavonoids with other components of the venom, as the inhibitory effects of flavonoids are not specific to hyaluronidase... 

All eight natural prenyl-flavones evaluated by Reddy et al. showed potent inhibitory effects on 5-lipoxygenase with IC50 from 0.36 to 4.3 pM. Artonin E isolated from the bark of Artocarpus communis Forst. (Moraceae) was the most potent dual LOX and COX inhibitor with IC50 values of 0.36 pM and 2.5 pM, respectively. It also inhibited leukocyte and platelet 12-... 

Citrus peel oils may also be used for their antioxidative, antitumor, and radicalscavenging activities. The radical-scavenging ability of citrus peel oil may help prevent free radical-induced and various chronic diseases (48, 55, 56). Monoterpenes from volatile components and polymethoxylated flavones from nonvolatile residues have been reported to be effective inhibitors of tumor cell growth, implicating that citrus peel oils may be good cancer preventive food additives (57-59). Furthermore, citrus peel oils are useful to alleviate pain from burnt skin (60). Demonstrating anxiolytic and sedative effect, they could also be used in primary medical care against insomnia, anxiety, and epilepsy (61). 

Quercetin and other flavonoids are effective inhibitors of 02 -production by cells. Quercetin is a potent inhibitor of human neutrophil degranulation and 02 -production, and also inhibits the phosphorylation of neutrophil proteins accompanying neutrophil activation by phorbol myristate acetate. Quercetin can also suppress lipid peroxidation in several biological systems, such as mitochondria, microsomes, chloro-plasts, and erythrocytes. Silymarin, a 3-OH flavone present in Silybum marianum (the European milk thistle), protects rat liver mitochondria and microsomes from lipid peroxide formation induced by Fe " "-ascorbate and NADPH-Fe -ADP systems. Soybean isoflavonoids have shown antioxidative potency... 

As for flavones, or isoflavones, mentioned previously, the prefix iso- signifies a similarity or, more exactly, the same chemical composition but a different structure, with different physical and chemical properties. According to a letter and litraature search presented by Sally Fallon and Mary G. Enig in the July 2004 Townsend Letter for Doctors Patients, cited elsewhere, the soy isoflavone genistein has been found to act as an inhibitor for tyrosine kinase. However, it has also been found to damage the DNA and to have adverse estrogen-like effects. Apparently, there is a trade-off. 

---