JBC: Intoxicating fragrance as valium substitute?

jasmine gardeniaJuly 12, 2010 -- Instead of a sleeping pill or a mood enhancer, a nose full of a fragrance from Gardenia jasminoides could help, according to researchers writing in the Journal of Biological Chemistry.

In collaboration with Dr. Olga Sergeeva and Professor Helmut Hass from the Heinrich Heine University in Düsseldorf, researchers from Ruhr-Universität-Bochum led by Professor Hanns Hatt have discovered that the two fragrances vertacetal-coeur (VC) and a chemical variation (PI24513) have the same molecular mechanism of action and are as strong as the commonly prescribed barbiturates or propofol. In the study, the fragrances were shown to soothe, relieve anxiety and promote sleep. The researchers have now been granted a patent for their discovery.

Drugs enhance the effect of the neurotransmitter GABA

Benzodiazepines, barbiturates and anesthetics such as propofol act via specific adhesion sites on receptors that lie at contact points of nerve cells (synapses) in the brain and increase the effect of the naturally occurring neurotransmitter GABA (gamma-aminobutyric acid). In order to act like body's neurotransmitter GABA, the chemical would have to be administered at a high dose, but even lower doses were sufficient to increase the effect of endogenous GABA two to threefold.

Fragrances instead of tablets

The researchers performed a screening study in which they tested hundreds of fragrances to determine their effect on GABA receptors in humans and mice. Two fragrances vertacetal-coeur (VC) and a chemical variation (PI24513) were the strongest: they were able to increase the GABA effect by more than five times and thus act as strongly as the known drugs. A "cross check" with genetically-modified GABA receptors in transgenic mice which were modified to no longer responded to propofol confirmed that the mechanism of action is the same for the fragrance and the propofol: the altered receptor no longer responded to the fragrances or the known drugs.

Fragrances for sleep disorders and stress

Behavioral tests with mice in Lübbert's laboratory then eliminated the last doubts concerning the possible use of  the fragrance as a sedative. Injected or inhaled, the fragrances generated a calming effect. When placed in a plastic cage with a high concentration of the fragrance, the mice ceased all activity and sat quietly in the corner. Electrophysiological measurements of neurons in the brain areas responsible for the sleep-wake cycle showed that the GABA-effect on those nerve cells was enhanced by the fragrances.

"Applications in sedation, anxiety, excitement and aggression relieving treatment and sleep induction therapy are all imaginable. The results can also be seen as evidence of a scientific basis for aromatherapy,"  Hatt said. By changing the chemical structure of the scent molecules, the researchers hope to achieve even stronger effects.

Citation

Fragrant dioxane derivatives identify β1 subunit-containing GABAA receptors. O. A. Sergeeva, O. Kletke, A. Kragler, A. Poppek, W. Fleischer, S. R. Schubring, B. Goerg, H. L. Haas, X.-R. Zhu, H. Luebbert, G. Gisselmann, H. Hatt. F. Journal of Biological Chemistry, 2010; DOI: 10.1074/jbc.M110.103309

Recent JBC papers from this group

Activation of an Olfactory Receptor Inhibits Proliferation of Prostate Cancer Cells. Neuhaus EM, Zhang W, Gelis L, Deng Y, Noldus J, Hatt H. Journal of Biological Chemistry 2009 Jun 12;284(24):16218-25.

Press release courtesy of Ruhr-Universität-Bochum

Image adapted from Erin Silversmith

Hanns Hatt at Ruhr-Universitat-Bochum