"The results pave the way for the development of novel anti-inflammatory drugs for a variety of illnesses and symptoms, such as headache, swelling, redness and inflammation," said Craig Crews, associate professor of molecular, cell and developmental biology, chemistry and pharmacology at Yale.
Feverfew, which is commonly used as an alternative medicine for migraine headaches, and some other anti-inflammatory medicinal herbs, are rich in a group of compounds thought to mediate the anti-inflammatory nature of these plants. The anti-inflammatory component in feverfew is called parthenolide.
Led by Crews, the research team set out to identify the molecular basis of parthenolide’s anti-inflammatory activity. Through a combination of chemical and biochemical approaches, the team made a derivative of parthenolide, which they used to look for proteins that bind to parthenolide. They found that IkappaB Kinase was one such binding protein, which is responsible for inflammation.
"We showed that the binding disrupted the protein’s ability to function, and we also were able to identify the part of the protein to which the compound binds," said Crews, whose study results are published in the August issue of Chemistry and Biology. "Now that we have identified one inhibitor of this protein, that information can be used to develop additional inhibitors. This is important because a single inhibitor may not always make a successful drug due to side effects, so it’s always useful to have a series of inhibitors."
Other Yale researchers on the study included Benjamin H.B. Kwok, Brian Koh, MacKevin I. Ndubuisi and Mikael Elofsson.
Crews can be contacted at 203-432-9364.