Cheer up

August 15, 2000

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

Please mention new scientist as the source of this story and, if publishing online, please carry a hyperlink to:

New Scientist

Related Enzyme Articles from Brightsurf:

Repairing the photosynthetic enzyme Rubisco
Researchers at the Max Planck Institute of Biochemistry decipher the molecular mechanism of Rubisco Activase

Oldest enzyme in cellular respiration isolated
Researchers from Goethe University have found what is perhaps the oldest enzyme in cellular respiration.

UQ researchers solve a 50-year-old enzyme mystery
Advanced herbicides and treatments for infection may result from the unravelling of a 50-year-old mystery by University of Queensland researchers.

Overactive enzyme causes hereditary hypertension
After more than 40 years, several teams at the MDC and ECRC have now made a breakthrough discovery with the help of two animal models: they have proven that an altered gene encoding the enzyme PDE3A causes an inherited form of high blood pressure.

Triggered by light, a novel way to switch on an enzyme
In living cells, enzymes drive biochemical metabolic processes. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics.

A 'corset' for the enzyme structure
The structure of enzymes determines how they control vital processes such as digestion or immune response.

Could inhibiting the DPP4 enzyme help treat coronavirus?
Researchers and clinicians are scrambling to find ways to combat COVID-19, including new therapeutics and eventually a vaccine.

Bacterial enzyme could become a new target for antibiotics
Scientists discover the structure of an enzyme, found in the human gut, that breaks down a component of collagen.

Chemists create new artificial enzyme
Rajeev Prabhakar, a computational chemist at the University of Miami, and his collaborators at the University of Michigan have created a novel, synthetic, three-stranded molecule that functions just like a natural metalloenzyme, or an enzyme that contains metal ions.

First artificial enzyme created with two non-biological groups
Scientists at the University of Groningen turned a non-enzymatic protein into a new, artificial enzyme by adding two abiological catalytic components: an unnatural amino acid and a catalytic copper complex.

Read More: Enzyme News and Enzyme Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to