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Relaxing with Lignan

Researchers discover why valerian calms us down

Hippocrates knew long ago that valerian calms people down and helps them to sleep. However, until recently it was a mystery how it did this. Pharmaceutists at the University of Bonn have now identified a substance which is probably partly responsible for this sedative effect. The substance, which belongs to the group of lignans, latches on to specific receptors in the brain which control the body's sleeping and waking rhythms. Caffeine affects the same type of receptor, but has the opposite effect. The researchers are now trying to copy a simplified version of the substance chemically, thereby making it even more effective.

There are various chemicals in the brain which bring on a feeling of tiredness, one of them being the chemotransmitter GABA. Until recently it was assumed that somehow valerian intervenes in the GABA regulatory circuit. Yet there is also a completely different 'tiredness molecule', adenosine: 'Adenosine is sleep-inducing,' says Christa Müller, Professor of Pharmaceutical Chemistry at Bonn. 'If animals are continually deprived of sleep, more and more accumulates in their brain.' The molecule attaches itself to specific nerve cell receptors, the adenosine receptors of type A1. It thereby triggers a chain reaction, resulting in drowsiness. Its opposite number, caffeine, can attach itself to the selfsame receptors. However, just as the wrong piece of a jigsaw puzzle cannot lead to the right picture, caffeine merely blocks the A1 receptors but does not bring about a reaction. The result is that the coffee drinker becomes more wide awake.

'Relaxed' brain waves

When, therefore, Professor Müller came across a publication which described the way valerian extract can attach itself to adenosine receptors, it made her sit up. 'We repeated the experiments and were able to confirm that aqueous alcoholic full extracts from the valerian root can attach themselves to the A1 receptor, at least in the brains of rats. What is more, we were able to show for the first time that the extract activates the receptors rather like adenosine does. Experiments with genetically produced human receptors had a similar result.' Now even Zeller, the Swiss pharmaceuticals company, showed interest. In a clinical study Zeller scientists measured the brain waves of just under 50 test subjects. After caffeine was ingested the alpha waves signalling relaxation levelled out; by contrast, the beta waves, signs of nervousness, became more marked. When valerian extract was administered, this effect was neutralised - an additional indication that the plant does in fact affect the A1 receptor.

However, the Bonn team did not yet know which substance attaches itself to the receptors. Contact with a research team in Marburg finally put them on the right track. The Marburg team had demonstrated that valerian contains different compounds from the lignan group. Lignans are natural substances which occur in many higher plants. Together with her assistant Dr. Britta Schumacher, Professor Müller unravelled more of the lignan fractions. She explains: 'In doing so, we discovered a previously unknown compound which can attach itself to the A1 receptor and bring about a similar reaction to adenosine.'    


Adenosine is bad for the heart

Adenosine is not, in itself, suitable as a sedative, since it is decomposed in seconds. Stable adenosine derivatives are also problematical: as there are also A1 receptors in the myocardium, albeit far fewer than in the brain, they may lead to myocardial paralysis. 'Our lignan, in contrast, is a partial agonist, i.e. it only kicks in when there is a high density of receptors in the brain,' the professor explains. In addition, special transport molecules appear to ensure that the lignan enters the brain easily.

As yet it is still completely unclear why the lignan is tolerated by the A1 receptor - the substance has hardly any similarity to adenosine. The Bonn researchers now intend to attempt to strip down the molecule such that only those parts which are essential for its specific effect are left. 'Then we can start to copy this slimmed-down version in the lab and possibly modify it so that it becomes even more effective.'


Contact person:
Professor Christa Müller
Pharmaceutical Institute of the University of Bonn
Tel.: ++49-228-732301
E-mail:
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Www: http://www.pharma.uni-bonn.de/pharmchem/

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Professor Müller and Dr. Jörg Hockemeyer during the extraction.
Photo: Frank Luerweg / Uni Bonn
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