Membranes flavonoid interactions with

Flavonoids bear different degrees of hydroxylation, polymerization, and methylation that define both specific and nonspecific interactions with membrane lipids. Molecule size, tridimensional structure, and hydrophili-city/hydrophobicity are chemical parameters that determine the nature and extent of flavonoid interactions with lipid bilayers. The hydrophilic character of certain flavonoids and their oligomers endows these molecules with the ability to bind to the polar headgroups of lipids localized at the water-lipid interface of membranes. On the other hand, flavonoids with hydrophobic character can reach and cross the lipid bilayer. In this section, we will discuss current experimental evidences on the consequences of flavonoid interactions with both the surface and the hydrophobic core of the lipid bilayer. 

Flavonoids can also interact with membrane proteins, such as those functioning as receptors, transporters, channels, and enzymes, and potentially affect their biological activities. A summary of recent advances on the study of flavonoid interactions with plasma membrane proteins is presented in Table 4.2. 

The affinity of flavonoids for phospholipid membranes has been unequivocally demonstrated by many authors. Many biological functions of these compounds are also believed to be the result of flavonoid interactions with cell membranes. Partition coefficients for a large group of flavonoids between water and olive oil were determined, and it was shown that the hydrophobic-ity of the compounds is inversely proportional to the number of OH groups. 

In addition, some flavonoids can differentially interact with membrane polar surfaces or penetrate into the bilayer, depending on certain characteristics of the reaction milieu. This is the case of quercetin, a flavonoid that at acidic pH is deeply embedded into planar lipid bilayers [Movileanu et al., 2000], while at... 

The finding that water-soluble flavonoids could exert their beneficial properties at the hydrophobic portion of the membrane was also observed in in vivo studies and in cells in culture. For example, erythrocytes obtained from animals fed a flavanol- and procyanidin-rich meal showed reduced susceptibility to free-radical-mediated hemolysis [Zhu et al., 2002]. Consistently, we demonstrated that procyanidin hexamers, which interact with membranes but would not be internalized, protected Caco-2 cells from AMVN- and bile-induced oxidation [Erlejman et al., 2006]. When liposomes were preincubated with a series of flavonoids with diverse hydrophobicity, not only hydrophobic flavonoids prevented AMVN-mediated lipid oxidation but also the more hydrophilic ones [Erlejman et al., 2004]. Similarly to what was previously found in liposomes, the protective effects of flavonoids against AMVN-supported oxidation was strongly associated with their capacity to prevent membrane disruption by detergents, supporting the hypothesis of a physical protection of membranes by preventing oxidants to reach fatty acids. 

The final chapter, The Role of the Membrane Actions of Phenothiazines and Flavonoids as Functional Modulators by K. Michalak, O. Wesolowska, N. Motohashi and A. B. Hendrich, presents a very comprehensive review on important biological effects of phenothiazines and flavonoids due to interactions with membrane proteins and the lipid phase of membranes. The discussion includes the influence of these heterocycles on model and natural membranes, modulation of MDR transporters by these heterocycles, and the effects of these hetero cycles on ion channel properties. This review may attract much interest from medicinal and pharmaceutical chemists as well as heterocyclic chemists in the life science fields. 

Very recently, we reviewed the role of membrane action of flavonoids. The structure of flavonoids enables specific interactions with different membrane proteins (multidrug transporters, voltage-gated and chemically activated ion channels) and also nonspecific interactions with the lipid phase of membranes [8]. 

Chelating activity gives another possibility to flavonoids to interact with the oxidation of membrane lipids, and it is considered important for... 

---