Flavonoids inhibition

Flavonoids inhibit cytiokine-indnced endothelial cell adhesion protein gene expression American Journal Patholology 147, 278-92. 

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). 

Effects of Allelochemlcals on ATPases. Several flavonoid compounds inhibit ATPase activity that is associated with mineral absorption. Phloretin and quercetin (100 pM) inhibited the plasma membrane ATPase Isolated from oat roots (33). The naphthoquinone juglone was inhibitory also. However, neither ferulic acid nor salicylic acid inhibited the ATPase. Additional research has shown that even at 10 mM salicylic acid inhibits ATPase activity only 10-15% (49). This lack of activity by salicylic acid was substantiated with the plasma membrane ATPase Isolated from Neurospora crassa (50) however, the flavonols fisetln, morin, myricetin, quercetin, and rutin were inhibitory to the Neurospora ATPase. Flavonoids inhibited the transport ATPases of several animal systems also (51-53). Thus, it appears that flavonoids but not phenolic acids might affect mineral transport by inhibiting ATPase enzymes. 

Effects of Allelochemlcals on ATP Supply. Allelochemlcals might decrease the ATP content of tissue by either increasing ATP utilization or decreasing ATP production. Some allelochemlcals that inhibit mineral absorption decrease ATP content of plant tissues. Salicylic acid decreased the ATP content of oat roots in a pH dependent manner (Figure 3). This result suggested that mitochondrial production of ATP was decreased in the tissue. On the other hand, Tillberg (38) found that salicylic acid and cinnamic acid increased the ATP content of Scenedesmus. Various flavonoids inhibited ATP production by mitochondria Isolated from cucumber (Cucumls satlvus L.) hypocotyls (54). Flavones such as kaempferol were more inhibitory than the corresponding flavanones. Substituted cinnamic acids such as caffeic acid were not inhibitory. 

The family Droseraceae consists of four genera and about 100 species of perennial herbs, of which Drosera burmannii Vahl, Drosera rotundifolia L, Drosera indica L., and Drosera peltata Sm. are used in Asia for the treatment of cough. Naphthoquinones and flavonoids, which occur in this family, have not been fully studied for pharmacology, and it appears that flavonoids inhibit human neutrophil elastase, hence the potential for the treatment of inflammation. 

Kim MH. 2003. Flavonoids inhibit VEGF/bFGF-induced angiogenesis in vitro by inhibiting the matrixdegrading proteases. J Cell Biochem 89(3) 529-538. 

In addition to xanthine oxidase, flavonoids are able to inhibit the activity of a wide range of enzymes. These inhibitory effects of flavonoids may depend both on their free radical scavenging and chelating properties. Thus, it has been shown that flavonoids inhibit... 

Middleton E Jr, Drzewiecki G. (1984). Flavonoid inhibition of human basophil histamine release stimulated by various agents. Biochem Pharmacol. 33(21) 3333-38. 

Song, J., Kwon, O., Chen, S., Damwala, R., Eck, P., Park, J.B., and Levine, M., Flavonoid inhibition of sodium-dependent vitamin C transporter 1 (SVCTl) and glucose transporter isoform 2 (GLUT2), intestinal transporters for vitamin C and glucose, J. Biol. Chem., 277, 15252, 2002. 

Iwashita K, Kobori M, Yamaki K, Tsushida T. Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. 2000 64(9) 1813-1820. 

Katayama K, Masuyama K, Yoshioka S, Hasegawa H, Mitsuhashi J, Sugimoto Y. 2007. Flavonoids inhibit breast cancer resistance protein-mediated drug resistance Transporter specificity and structure-activity relationship. Cancer Chemother Pharmacol 60 789-797. 

Schuier M, Sies H, Illek B, Fischer H. 2005. Cocoa-related flavonoids inhibit CFTR-mediated chloride transport across T84 human colon epithelia. J Nutr 135 2320-2325. 

Tauber AI, Fay JR, Marietta MA. 1984. Flavonoid inhibition of the human neutrophil NADPH-oxidase. Biochem Pharmacol 33 1367-1369. 

FIGURE 31.1 Flavonoids inhibit and decrease gastric secretion. 

Flavonoids Inhibition of virus adsorption by flavonoids such as (-) epicatechin and its 3-0-gallate has been attributed to an irreversible interaction with gpl20 (although these compounds are also known as reverse transcriptase inhibitors). 

Aviram, M. et al., Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases studies in atherosclerotic mice and humans, Drugs Exp. Clin. Res., 28, 49-62, 2002. 

In contrast to many other potassium channels (see below), the inward rectifying K+ channels in guinea pig ventricular myocytes were directly blocked by genistein (42) and daidzein (40) [312]. Both flavonoids inhibited inward rectifying K+ current in a dose-dependent manner. The opposite effect (i.e., stimulation) was observed when the influence of naringenin (33) on the Ca2+-activated K+ channels of rat tail artery myocytes was studied [313]. Channel activation was dose-dependent and reversible after flavonoid wash-out. The final conclusion of this work was that the vasorelaxant effect of naringenin (33) could be due to activation of Ca2+-activated K+ channels. 

---