Flavonoids Found To Regulate Cell Processes, Enhance Health

These molecules bind to the protein actin, which is implicated in cell movement and cell division.

According to preclinical findings published in the October 2007 issue of the Biophysical Journal, the ability of actin to join to long chains is either suppressed or improved. Surprisingly, it has been shown that these substances also affect the rate at which genetic data are processed in the cell's nucleus.

A large family of plant pigments, the flavonoids, comprises over 6,000 structurally related substances found in fruit and vegetables of our daily diet. They appear to induce the positive health effects of green tea or red wine. However, their functional mechanisms are diverse and not well understood. This complicates the effective evaluation of their beneficial effects as well as possible health risks. Many scientists try to understand these mechanisms on a molecular level, hoping to learn from nature to design new compounds that can be used in therapies of cancer or heart diseases.

The recent study reports two surprising results that are related to the binding of flavonoids to the protein actin. Actin is one of the most examined and abundant proteins. Together with other biomolecules, it enables muscle contraction, changing the cell shape and separation of daughter cells during cell division. In 2005, biologists from the Technische Universität Dresden (Germany) were surprised to find that flavonoids can bind to actin in the nucleus of living cells.

Now, together with the biophysics group at the Forschungszentrum Dresden-Rossendorf (FZD; Dresden, Germany), the investigators established in the laboratory that flavonoids influence the growth of chains of actin molecules, a process that is linked to the cellular functions of actin. Flavonoids can strengthen or weaken this process. Amazingly, the same dependency on flavonoids was observed for the speed at which the genetic material is read from the DNA in the cell nucleus. These findings, according to Prof. Herwig O. Gutzeit, from the Technische Universität Dresden, demonstrate that the direct biologic effects of flavonoids on actin may also influence the activity of genes in a cell.

Biophysicist Dr. Karim Fahmy, from the Forschungszentrum Dresden-Rossendorf, was able to demonstrate the molecular mechanism by which flavonoids can affect actin functions. The flavonoids function as switches that bind to actin and promote or inhibit its functions. Using infrared spectroscopy, Dr. Fahmy evaluated the interaction of actin with the activating flavonoid epigallocatechin and the inhibitor "quartering.” This method is well suited for demonstrating structural alterations in large biomolecules without any interventions that may affect the extremely sensitive proteins. Upon addition of the selected flavonoids to actin, the structure of the actin changes in a dramatic and typical way. Depending on the type of flavonoid, the "actin switch” is set to increased or reduced functional activity.

The mechanism appears obvious to the scientists: the effects of the flavonoids are a function of their form. Actin itself is a flexible molecule, which clarifies why various flavonoids can bind to actin in a very similar way but nevertheless produce effects that range from inhibition to stimulation. Flexible flavonoids correspond to the structure of the actin and create complexes that improve actin functions.

More rigid flavonoids force the actin into a structure that is less compatible with its natural functions, thereby inhibiting actin-dependent cellular processes. Simulations of flavonoid binding to actin performed in the bioinformatics group of Dr. Apostolakis at the Ludwig-Maximilian University of Munich (Germany) identified the putative site where flavonoids interact with actin. The collaborative and highly interdisciplinary efforts allowed determining previously unknown structure-specific functional processes of flavonoids. This knowledge should help in the near the future in the search for compounds with improved effectiveness and specificity that can be used to modulate actin functions for therapeutic purposes.


Related Links:
Forschungszentrum Dresden-Rossendorf
Technische Universität Dresden