Dr. Gert Fricker is a biochemist and department head of the University of Heidelberg’s Institute of Pharmacy & Molecular Biology. He has worked for the Novartis drug company and does research that is largely funded by grants from that and other industrial concerns. He’s one of the directors of Heidelberg’s technological park, which has some ties to Panama’s City of Knowledge, and thus was here mainly to deal with that latter relationship. However, on January 18 he found the time to give one of the Smithsonian Tropical Research Institutes Tuesday science lectures, attracting a crowd of City of Knowledge folks along with the usual Tupper Center crowd.
Fricker talked about the interactions between herbal remedies and manufactured drugs, in a talk that ranged from common good sense about negative possibilities to promising experiments with helpful interactions.
Despite his long-standing ties with pill manufacturers, or possibly because of them, Fricker maintains an interest in herbal as well as standard medicine, and is engaged in ongoing studies of plants used in traditional Chinese healing. He maintained that despite all prejudices, phytotherapy (herbal medicine) is a recognized part of modern medicine. For one thing, herbal medicine is now estimated to be a $16 billion per year industry. Plus he noted, it is believed that over millennia humans may have adapted to plant medications and that these substances typically have fewer undesirable side effects.
But it is now known that there are down sides to herbal medicines, starting with wide variations in the potencies of many of the commonly used substances.
One of the problem relationships between herbal cures and standard medicines, Fricker explained, can arise when people afflicted with depression use St. John’s wort --- concoctions made from plants of the genus Hypericum --- to chase away the blues. Noting the many forms in which this herbal remedy is prepared and that it is one of the most studied and best understood plant medicines, he explained that it active ingredients are generally better described as suspected rather than known, and that the amounts of these vary widely.
Dr. Fricker also noted that St. John’s wort inteferes with the effects of the AIDS drug indinavir, with warfarin and other anti-coagulants, with oral contraceptives and with the anti-rejection drug cyclosporin.
Why? Because St. John’s wort affects enzymes in the liver, intestines and kidneys, for one thing, thus affecting the body’s absorption of various medications. And that’s not a radical new discovery --- doctors nowadays take much more detailed information about the substances one ingests, whether as foods, beverages or medicines, because it’s known that herbal medicines, teas, soybean products and grapefruit juice are among the many things that affect drug uptakes.
More specifically, St. John’s wort strengthens the blood-brain barrier, a biochemical blockade that keeps most substances from getting out of capillaries into brain tissues. It has been found that the herbal remedy induces the production of p-Glycoprotein, a substance naturally produced in the human body, which concentrates in the endothelial cells of capillaries to block the transfer of certain chemicals into the brain and several other organs as well. The substance also plays a role in the body’s resistance to the spread of cancers.
(Why doesn’t the blood-brain barrier work against all chemicals? One reason, Fricker noted, is that certain chemicals that are substrates of p-Glycoprotein rather freely filter right through, and one of these chemicals is ethyl alcohol --- the active ingredient in booze --- which is why the blood-brain barrier is not a natural defense against drunkenness.)
So how does a scientist study the chemistry of the blood-brain barrier? One of the ways that scientists at the University of Heidelberg do it is to obtain fresh pig brains from the local slaughterhouse, slice them and preserve them in certain ways and use them to observe how the still functioning endothelial cells work in different conditions. By means of flourescent markers and microscopes, researchers can see whether a substance is kept within the capillaries or diffused into the brain cells.
Viewed that way, it can be readily observed that St. John’s wort helps to keep certain medications in the blood stream and out of the brain.
But of course, there are times when a healer wants to get a medication past the blood-brain barrier, as dangerous as it might be.
(How dangerous? It turns out that most substances that suppress the blood-brain barrier also affect similar barriers protecting other organs, and that what desirable things they may do in the brain can cause catastrophic failures of these other organs. For this reason, Fricker noted, the drug companies shy away from these kinds of drugs and the potential liabilities that come with them.)
Not too many years ago, Fricker noted, medicine discovered the properties of taxol, a product derived from the bark of Pacific yew trees. It’s a very good herbal remedy for many breast cancers. The supply problem was at first a huge problem --- it takes the bark of six trees to provide the taxol to treat one person --- but then ways of extracting the substance from the needles of several related evergreens made the stuff more available and affordable.
Breast cancers are tumors of the fatty tissues, and another organ composed of fatty tissues that’s subject to deadly tumors is the brain. However, the first attempts to use taxol against brain tumors proved ineffective. This, even though taxol is a “lipophilic” substance, and most such fat-loving compounds readily cross the blood-brain barrier. Taxol is just one of the exceptions to that rule, as test on pig brains revealed.
But what if you can block the body’s production of p-Glycoprotein? When you do that in a pig brain, taxol gets out of the capillaries and into the brain tissue.
So an experiment was devised using mice, divided into three groups. The control group was not medicated in anyway. Another group was given taxol only. The third group was given Valspodar, a medication that suppresses p-Glycoprotein, and then a bit later taxol. But first, all of the mice had human brain tumor cells injected into their brains, where the tumors took hold and untreated tended to kill the mice in a little more than a month’s time.
After 35 days all the mice were killed and the progression of their brain tumors was noted. In both the control group and the group that received taxol only, the tumors tended to be well advanced. But in the group that received Valspodar and then taxol, the brain tumors were more than 90 percent smaller than those of the other two groups.
“This, to my knowledge, was the first evidence that taxol is useful for brain tumors,” Fricker said. It will, of course, take many more studies before such a treatment for human brain tumors is perfected, tested and approved, if it ever is.
But this is an example of the flip side of the undesirable interaction between St. John’s wort and many standard medications. Here an industrial product can interact in a way that makes an herbal remedy effective --- at least in mice --- when alone the plant substance wouldn’t be.
