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form of flavonoid-containing dietary supplements or herbal products. Increasing knowledge about their beneficial health effects is causing increased flavonoid consumption. However, for many years it has been known that the spectrum of effects exerted by flavonoids is very broad. Therefore, careful evaluation of the biological activity of flavonoids seems to be important for the proper determination of their safety.
As was shown in the present review, flavonoids can interact with both lipid and protein components of biological membranes and alter their properties. Interactions with lipids are, in most cases, limited to the polar region of the lipid bilayer; however, the depth of membrane penetration by flavonoids depends on their structure. Most flavonoids studied decrease membrane fluidity. The main factor governing the strength of flavonoid-lipid interactions seems to be the lipophilicity of the flavonoid molecules. It seems also that the presence of the 3-hydroxyl group and the 2,3 double bond are of utmost importance for the antioxidative activity of flavonoids.
Flavonoids interact also with membrane transporter proteins and thus inhibit the drug transport responsible for MDR. The structural features of flavonoids that are propitious for their inhibitory properties are almost the same as those that bring about their antioxidative activity. The presence of 3- or 5-hydroxyl groups and the 2,3 double bond are also important. In some cases prenylation of the flavonoid molecule increases its inhibitory potency.
Knowledge about flavonoid interactions with membrane components seems to be sufficient to predict the structure of potential flavonoid-based drugs and to harness the desired biological effects. The same knowledge should allow the possible side-effects associated with flavonoid usage to be minimized.
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