St John’s wort provides a model to develop effective medication
Pharmacists at FAU are looking for new ways to treat depression. The model for these investigations is provided by a well-known medicinal plant, St John’s wort, which contains the antidepressive agent hyperforin that the researchers aim to develop further. The project, which forms part of the European research consortium HYPZITRP, has received 184,000 euros in funding from the Federal Ministry of Education and Research (BMBF) for the next three years.
Depression is one of the most significant chronic illnesses in developed countries such as Germany. It puts considerable pressure on patients which has serious consequences for their professional and every-day lives. In addition to the adverse effects that depression has on individuals, the illness puts great strain on the economy due to absences and early retirement. ‘Despite intensive research, we still only have a partial understanding of how depression develops,’ says Prof. Dr. Kristina Friedland, Chair of Molecular and Clinical Pharmacy at FAU. ‘This is why we are focusing on two different areas – researching molecular processes in the human body and developing effective medications.’
St John’s wort: used for centuries
St John’s wort (Latin: Hypericum perforatum) has been used to improve mood and treat mild to moderate depression for centuries. Hyperforin, the active agent contained in St John’s wort, helps to regulate neurotransmitters such as serotonin, dopamine and noradrenaline. ‘What we believe to be key to this approach is that the antidepressant effect of hyperforin is based on the activation of an ion channel, the TRPC6 channel – unlike other forms of medication which are currently on the market,’ explains Kristina Friedland. ‘Unfortunately, the natural extract is not strong enough to be used to treat severe depression. Hyperforin also triggers the formation of the CYP3A4 enzyme which forms a key part of metabolisation. This can cause problematic drug interactions. It is also unstable when it is isolated from the extract.’
In light of this, the Erlangen-based pharmacists have set themselves an ambitious goal. They want to develop and test hyperforin analogues – chemically produced active agents which are based on the structure of hyperforin. ‘We are looking for derivatives which are considerably more stable and more effective than the natural active agent in St John’s wort and which also interact less with other medications,’ says Kristina Friedland. The BMBF has provided the FAU research group with 184,000 euros in funding in order to develop this kind of structure. The efficacy of the hyperforin analogues will be tested using methods such as cell models and animal testing.
A research consortium exploring molecular processes
In the international research consortium HYPZITRP – HYP stands for hyperforin, ZI for zinc and TRP for TRPC6 channels – researchers are working not only on developing antidepressants but also on understanding the molecular mechanisms and changes in communication of nerve cells in the brain due to the illness. A working group at CEA in Grenoble in France is investigating the role of zinc, as sufferers of depression have been shown to have less zinc in their cells than healthy people. Meanwhile a group of researchers at the University of Krakow in Poland is using animal models to study the effect that hyperforin analogues have on TRPC6 channels, through which nerve cells are activated and neurological reactions are triggered. ‘At the moment, we do not know enough about the pathophysiology of depression. We need to understand this in order to develop medications which are more stable and more effective, and have less side effects,’ explains Kristina Friedland.
With over 38,000 students, 653 professorships and 13,000 employees, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), founded in 1743, is one of the largest universities in Germany – and, as recent rankings show, among the most successful and strongest research universities. Currently ranked 10th in the DFG Funding Ranking, FAU belongs to the same league as the German ‘Universities of Excellence’. In addition to the Cluster of Excellence ‘Engineering of Advanced Materials’ (EAM) and the Graduate School of Advanced Optical Technologies (SAOT), which was founded as part of the Excellence Initiative, FAU currently has more than 30 co-ordinated programmes with DFG funding.
The University of Erlangen-Nürnberg offers around 240 degree programmes, among them 5 Bavarian Elite Master’s degree programmes and more than 32 programmes with a distinct international focus. No other German university offers such a broad and interdisciplinary range of subjects on all qualification levels. FAU students enjoy global mobility through over 500 partnerships with higher education institutions in more than 70 countries.
Prof. Dr. Kristina Friedland
Phone: +49 9131 8529550