Flavonoids secretion

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a chloride (CF) channel characterised by chloride permeability and secretion, and also by the regulation of other epithelial ion channels (Eidelman et al, 2001). Mutations in the CFTR gene lead to an impaired or absent Cl conductance in the epithelial apical membrane, which leads to defective Cl secretion and absorption across the epithelium. Genistein (Illek et al, 1995 Weinreich et al, 1997) and other flavonoids (Illek and Fisher, 1998) have been shown, in different animal and tissue models, to activate wild-type CFTR and CFTR mutants by (Eidelman et al, 2001 Roomans, 2001 Suaud et al, 2002) ... 

Fig. 1. Schematic diagram showing the different mechanisms of action proposed for the antiulcer action of flavonoids. 1. Blockade of add secretion by decreasing histamine production or inhibiting the proton pump. 2. Bactericidal effect on H. pylori. 3. Antioxidative activity by scavenging free radicals and preventing ROM formation. 4. Potentiation of the mucosal protective factors. PAF platelet activating factor ROM reactive oxygen metabolites H2 histamine receptor 2 M muscarinic receptor G gastrin receptor.

In conclusion, the effects of flavonoids on intestinal motility and secretion can justify their antidiarrheal properties, although more research in this field is required in order to fully understand the mechanims of action involved. 

Borradaile NM, de Dreu LE, Huff MW. 2003. Inhibition of net HepG2 cell apolipo-protein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. Diabetes 52 2554-2561. 

FIGURE 31.1 Flavonoids inhibit and decrease gastric secretion. 

Pearce, F. L., Befus, A. D., and Bienenstock, J. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol, 73(6), 819-823, 1984. 

Wilcox, L.J., Borradaile, N., Kurowska, E., Telford, D.E., and Huff, M.W. 1998. Naringenin, a citrus flavonoid, markedly decreases apoB secretion in HepG2 cells and inhibits acyl CoA cholesterol acyltransferase. Circulation 98, 531—537. 

Legumes also secrete antagonists that inhibit the flavonoid-mediated activation of nodulation genes (Table 2).63 64 Some act as inducers in another symbiotic system. Antagonists generally have structures similar to those of inducers and inhibition can be overcome by increasing the concentration of inducers, hence they are considered as competitive inhibitors.63... 

---