A safer form of St John's wort is on its way
A natural remedy is about to get a revamp. Researchers in the US and Britain are trying to develop a form of the popular antidepressant St John's wort that has fewer adverse effects.
Known as nature's Prozac, the extract of the plant Hypericum perforatum is the second most popular herbal supplement in the US, and in Europe it has long been prescribed by doctors to combat depression. The herb has few side effects--although in strong sunlight it can cause cataracts (New Scientist, 24 July 1999, p 24)--and some studies have suggested that it is as least as effective as other antidepressants.
But earlier this year, doctors warned that St John's wort--which contains more than two dozen active ingredients, most of which haven't been studied--decreases the effectiveness of a wide range of drugs, including birth control pills and antibiotics. The discovery by Steven Piscitelli of the US National Institute of Mental Health in Maryland that it even interferes with anti-HIV drugs led the Federal Food and Drug Administration to put out a warning advising against its use without consulting a doctor.
To find out how the herbal supplement interferes with these drugs, two independent teams studied the commercially available extracts of St John's wort. They discovered that hyperforin--a component responsible for much of the antidepressant activity--also stimulates the production of a liver enzyme called CYP3A (Journal of Endocrinology, vol 166, p R11).
"It's crucial for the proper metabolism of the body's hormones, synthetic steroids and many drugs," says Krishna Chatterjee of Cambridge University. But if levels of the enzyme are too high, drugs are broken down too fast to be effective.
Production of CYP3A is boosted when substances binds to the so-called steroid X receptor in liver cells. Various hormones bind to this receptor, so the higher their concentrations, the faster they are broken down--a negative feedback loop that regulates their levels.
But Chatterjee's group found that hyperforin also binds strongly to the receptor. "It can out-compete other drugs that normally bind to the steroid X receptor," he says. Steven Kliewer of Glaxo-Wellcome in North Carolina and his colleagues got similar results (Proceedings of the National Academy of Sciences, vol 97, p 7500).
Both Chatterjee's group at Cambridge and Glaxo-Wellcome now plan to make a synthetic version of hyperforin that won't bind to the steroid X receptor but retains its antidepressant activity. "But it won't be easy," says Kliewer, "because we first need a better understanding of St John's wort."
Author: Diane Martindale
New Scientist issue: 19 August 2000
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