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Tuesday, 9 October, 2001, 09:42 GMT 10:42 UK
Pine cone source for stroke drug
brain image
Damage can be widespread following stroke
A molecule extracted from green tea leaves or pine cones may be able to reduce the brain damage from strokes, say scientists.

Gallotannin, and nobotanin B - found in a Japanese flower - both cut the damage from a simulated stroke in mouse brain cells grown in the laboratory.

However, there is no guarantee that they will work as well in a real patient.

The hours following a stroke are crucial to the future prospects, or even survival of the patient.

The stroke itself is caused by a halt to the blood flow to brain cells, either caused by bleeding on the brain, or by a blood clot lodged in a vessel.

However, although this kills some brain cells, once the blood supply is restored in the subsequent hours, many more cells tend to die.

This destructive reaction is still not fully understood, although scientists have found that a chemical signalling system has a role.

Signalling mechanism

This is there to let a cell know that damage to DNA has occurred, and set to work repairing it.

However, after stroke, the signalling system can respond too efficiently, using up a chemical which the cell needs to produce energy. This can lead to the death of the cell.

What matters is whether or not you can get the drug to where it's needed, and we're optimistic that we will be able to make PARG inhibitors that can pass into the brain

Dr Raymond Swanson, UCSF
One body chemical with a role in this signalling process is called PARG (Poly-ADP-Ribose Glycohydrolase).

Its role is to clear up after another enzyme called PARP whose role is to mark out damaged areas - PARG breaks down PARP's chemical tags.

Scientists from the University of California in San Francisco believe that if they can find a way to inhibit PARG, they can call a halt to this destructive over-response.

And they have found that the two types of tannin appear to have promise as "PARG inhibitors".

Their work is published in the Proceedings of the National Academy of Sciences.

In their experiments, they tested their PARG inhibitors against mouse brain cells which had been treated with highly-toxic peroxide, which would normally cause widespread DNA damage.

Normally, this would kill more than 70% of them - however, with the chemicals added, fewer than 20% died.

Too bulky

However, currently, these tannin molecules are too big to cross the "blood-brain barrier" - a filter which stops large molecules entering the brain.

The team will now try to produce a smaller, active molecule which works the same way.

Dr Raymond Swanson, the lead author of the study, said: "What matters is whether or not you can get the drug to where it's needed.

"And we're optimistic that we will be able to make PARG inhibitors that can pass into the brain."

However, many scientists are already well advanced trying to make drugs which can inhibit PARP - the other enzyme which starts the signalling process.

Several pharmaceutical companies are already working on drugs to this end.

Dr Mike Threadgill, a Reader in Medicinal Chemistry from the University of Bath, said that while aiming for PARG instead was "less fashionable", it was certainly interesting.

"I can only speculate on how it might work - I would say that nine out of ten scientists are working on PARP.

"It seems like a PARP inhibitor is likely to reach the finishing line first."

See also:

03 Aug 01 | Health
'Ice baths' help stroke patients
22 Jul 01 | Health
'Treatment for stroke' hope
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