Scientists unravel mechanism behind valerian's calming effect
that appears to be partly responsible for the previously
unexplained sedative effect of valerian, a herbal native to Europe
and used for more than 2,000 years.
The researchers say that a lignan in valerian 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, according to the team. They are now trying to copy a simplified version of the substance chemically to increase its efficacy.
Sales of valerian products in Germany alone are thought to be worth around €100 million, and up to €300 million across Europe, according to Joerg Gruenwald of Phytopharm Consulting.
"There is already good science on this herb but all new evidence proving the efficacy of herbals helps to raise awareness and sales," he told NutraIngredients.com.
The herb is taken as a sleep aid and also a sedative for tension, stress and intestinal colic or cramps. Root extracts and oils are also used to flavour tobacco, alcoholic beverages and other food products.
Until recently it was assumed that valerian intervened in the GABA regulatory circuit. GABA is a chemotransmitter and one of various chemicals in the brain that bring on a feeling of tiredness.But the new research suggests that valerian works on a different 'tiredness molecule' called adenosine, targeting specific adenosine receptors of type A1 and triggering drowsiness.
Caffeine can also attach itself to the same receptors but it merely blocks the A1 receptors without causing a reaction. The result is that the coffee drinker becomes more wide awake.
Christa Müller, professor of Pharmaceutical Chemistry at Bonn, said: "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," she addd.
The work attracted the attention of Swiss pharmaceuticals companyZeller, which measured the effects of valerian on brain waves of around 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.
Joining up with researchers in Marburg allowed the Bonn team to identify the substance that attaches to the receptors. The Marburg team had demonstrated that valerian contains different compounds from the lignan group, found in many plants.
Professor Müller unravelled more of the lignan fractions and discovered a previously unknown compound, which can attach itself to the A1 receptor and bring about a similar reaction to adenosine.
Adenosine is not, in itself, suitable as a sedative, since it is decomposed in seconds. Stable adenosine derivatives are also problematical because there are also A1 receptors in the myocardium (the muscle layer in the heart), and although far fewer than in the brain, they may lead to myocardial paralysis.
"Our lignan, in contrast, is a partial agonist, meaning it only kicks in when there is a high density of receptors in the brain," explained Müller. In addition, special transport molecules appear to ensure that the lignan enters the brain easily.
It is still completely unclear why the lignan is tolerated by the A1 receptor - the substance has hardly any similarity to adenosine. But the Bonn researchers are now planning to strip down the molecule leaving only those parts which are essential for its specific effect.
"Then we can start to copy this slimmed-down version in the lab and possibly modify it so that it becomes even more effective," added Müller.
