Lecture: Nuclear Receptor's Role in
Herb-Drug Interactions
Dr. Steven Kliewer (left) with Dr. Stephen E. Straus, NCCAM Director
The potential for interactions between herbs and drugs is of interest to many researchers, clinicians, and consumers. Much of that interest is focused on St. John's wort, an herbal remedy for depression, which can affect the metabolism of various drugs--including birth control pills and drugs used to treat high blood pressure, depression, asthma, and immune system disorders.
"The question is," said Stephen Kliewer, Ph.D., "is St. John's wort unique, or is this going to come up with other herbs?" On October 26, 2004, Dr. Kliewer spoke at NIH on "Reverse Herbology: Predicting and Preventing Adverse Herb-Drug Interactions," as part of NCCAM's Distinguished Lectures in the Science of Complementary and Alternative Medicine. He is professor of molecular biology and pharmacology and holds the Nancy B. and Jake L. Hamon Distinguished Chair in basic cancer research at the University of Texas Southwestern Medical Center's Graduate School of Biomedical Sciences.
Dr. Kliewer's research has focused on nuclear receptors, proteins that set off certain body functions and play an important role in metabolism and disease. His study of PXR, a nuclear receptor for foreign substances (called xenobiotics), has led to an increased understanding of some herb-drug interactions, especially with St. John's wort.
When triggered, PXR sets off a series of reactions in the body to clear out potentially dangerous substances. While most nuclear receptors are triggered by specific substances, many different chemicals can set off PXR, making it "ideally suited to protect the body from a wide range of foreign chemicals," Dr. Kliewer said.
However, when drugs or herbs (such as St. John's wort) trigger PXR, this causes the body to speed up metabolism, resulting in potentially dangerous changes in drug levels in the body. By analyzing the types of substances that trigger PXR, Dr. Kliewer and other researchers can now predict what herbs are likely to interact with drugs. For example, Dr. Kliewer reported that recent studies have shown that guggulipid (a traditional Indian herb used to treat high cholesterol and obesity) and hops (an herb promoted for insomnia, anxiety, and indigestion) also trigger PXR.
"The important take-home message," Dr. Kliewer said, "is that we have the tools to predict and prevent this class of drug interactions."
To view a videocast of this lecture on the Internet, go to videocast.nih.gov, select "Past Events," and use "Search" to locate the lecture.
