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uni'wissen 02-2013_ENG

scientists compared the effects of the entire birch bark extract with those of the isolated pure substances. Detective Work on the Molecular Level Merfort and her team determined that the nat- ural substance already takes effect in the first phase of wound healing. When skin cells are damaged, they release certain mediators. These are substances that lead to a temporary inflam- mation. “This is not something bad. An inflam- mation is nothing other than a defensive reaction of the body and is an integral part of the healing process,” explains Merfort. The mediators in- clude messengers like chemokines: They attract phagocytes, which remove foreign bacteria and dead tissue. Several tests the Freiburg pharma- ceutical researchers conducted demonstrated that the birch bark extract does in fact increase the amount of mediators. Betulin, the main sub- stance of the extract, is primarily responsible for the reaction. The scientists performed these ex- periments on keratinocytes, the most common cell type in the outermost layer of skin. Derma- tologists at the University of Hamburg also test- ed the natural substance on a pig’s ear, since the skin of this animal is physiologically very similar to that of humans, and confirmed the findings. After demonstrating that the birch bark extract temporarily increases the amount of inflamma- tory mediators, the pharmaceutical researchers set out to find out what happens on the molecu- lar level. They went about it like detectives in search of clues. Since the amount of messen- gers present is linked directly to the lifespan of the messenger ribonucleic acid (mRNA), they in- vestigated whether the substance from the birch increases the half-life of mRNA. In order for the blueprint of a protein to be read by the genome, a gene first has to be translated into a strand of mRNA. The more mRNA a gene has and the longer it remains stable, the more of the protein it can produce. For example, the half-life of the mRNA of the messenger COX-2 tripled when the scientists added the birch extract to the cells. Again, betulin was responsible for the bulk of this reaction. The pharmaceutical researchers eventually found the molecular initiator of the reaction: the enzyme p38 MAPK. The birch substance acti- vates p38 MAPK, and the enzyme ensures that the mRNA remains stable longer. In order to be completely sure of this, the researchers added a p38 inhibitor to the human skin cells they had treated. This reduced the half-life again, proving that the enzyme is indeed the main reason why the birch bark extract works in the first phase of “It was an exciting and interesting project that enabled us to strengthen traditional plant remedies” Healing a wound, step by step: The human skin is composed primarily of keratinocytes (blue) and fibroblasts (green). In the first phase, the damaged cells release inflammatory mediators to attract scavenger cells (white) like granulocytes, phagocytes, and macrophages, which remove foreign bacteria (gray) and dead tis- sue. In the second phase, macrophages secrete growth factors, allowing the skin cells to proliferate, migrate into the wound, and close it. By the end of the third phase, the remodeling, the skin has restructured itself. The macrophages die off, and scar tissue forms (brown). Illustration: Tamara Klaas s s 26