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鈥檚 wort that
has fewer adverse effects.
Known as nature鈥檚 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鈥攁lthough in strong sunlight it can cause cataracts
(快猫短视频, 24 July 1999, p 24)
鈥攁nd some studies have suggested
that it is as least as effective as other antidepressants.
But earlier this year, doctors warned that St John鈥檚 wort鈥攚hich
contains more than two dozen active ingredients, most of which haven鈥檛 been
studied鈥攄ecreases 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.
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To find out how the herbal supplement interferes with these drugs, two
independent teams studied the commercially available extracts of St John鈥檚 wort.
They discovered that hyperforin鈥攁 component responsible for much of the
antidepressant activity鈥攁lso stimulates the production of a liver enzyme
called CYP3A (Journal of Endocrinology, vol 166, p R11).
鈥淚t鈥檚 crucial for the proper metabolism of the body鈥檚 hormones, synthetic
steroids and many drugs,鈥� 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鈥攁 negative feedback
loop that regulates their levels.
But Chatterjee鈥檚 group found that hyperforin also binds strongly to the
receptor. 鈥淚t can out-compete other drugs that normally bind to the steroid X
receptor,鈥� 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鈥檚 group at Cambridge and Glaxo-Wellcome now plan to make a
synthetic version of hyperforin that won鈥檛 bind to the steroid X receptor but
retains its antidepressant activity. 鈥淏ut it won鈥檛 be easy,鈥� says Kliewer,
鈥渂ecause we first need a better understanding of St John鈥檚 wort.鈥�