Previous research topics (selection):
Overview
Anti-inflammatory constituents of Asteraceae
Extracts of chamomile (Matricaria recutita L.) and yarrow (Achillea millefolium sl) possess anti-inflammatory properties. Chamazulene carboxylic acid (CCA) is a degradation product of sesquiterpene lactones of some Asteraceae. We discovered CCA to be a naturally occurring profen, structurally resembling the purely synthetic anti-inflammatory and analgesic drugs naproxen, ibuprofen, etc. We examined its configuration, stability, and anti-inflammatory activity in animal models, as well as its molecular mechanism of action. CCA showed selectivity for cyclooxygenase-2 (PGHS-2). After oral administration of matricin, the biogenetic precursor of CCA, to volunteers in a small clinical study, significant blood levels of CCA were observed. We also established an animal model to compare the topical anti-inflammatory properties of chamomile ingredients, mixtures thereof, chamomile extracts, and extracts of Asteraceae with related ingredients. Thus we determined the optimal combination, dosage and administration time of antiinflammatory Asteraceae ingredients.
Chamaviolin was reported to be a chamomile constituent. We showed it to be an artifact that was formed during work-up of the extract.
Cooperations:
Robugen GmbH Pharmazeutische Fabrik, Esslingen
Dr. Gerhard Fürstenberger, Forschungsgruppe Eicosanoide und Tumorentwicklung, Deutsches Krebsforschungszentrum, Heidelberg
Prof. Dr. Ronald Gust, Institut für Pharmazie, Freie Universität Berlin
PhD and Diploma Theses:
C. Oehler, Diploma Thesis (Pharmacy) Halle 2000
T. Buss, Diploma Thesis (Pharmacy) Halle 2001
A. Meyer, Diploma Thesis (Pharmacy) Halle 2003
T. Buss, PhD Thesis Marburg 2005
M. Ramadan, PhD Thesis Marburg 2005
C. Oehler, PhD Thesis Halle 2009
arachidonic acid mimetics
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) inhibit the oxidation of arachidonic acid by COX (= PGHS), and it is believed that their analgesic and anti-inflammatory properties are at least partially due to this. The competitive inhibition of COX by arylpropionic and arylacetic acid derivatives is based on their molecular mimicry of arachidonic acid. Since arachidonic acid derivatives were discovered to be endogeneous cannabis receptor ligands, we have cooperated with other reserach groups, researching the likely possibility that known COX inhibitory NSAIDs interact with the endocannabinoid system. We extended this hypothesis to drugs that get acylated metabolically with arachidonic acid. We were able to identify two arachidonic acid amides as new metabolites of the well-known potent analgesic metamizol (dipyrone), characterising them pharmacologically.
Cooperations:
Prof. Dr. Vincenzo Di Marzo and Dr. Luciano De Petrocellis, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy
Dr. Aron H. Lichtman, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
Bernhard Watzer, Mutter-Kind-Zentrum, Zentrum für Kinder- und Jugendmedizin, Pädiatrische Forschung, Labor für Instrumentelle Analytik, Marburg
Prof. Dr. Rolf Nüsing, Pharmazentrum Frankfurt, Institut für Klinische Pharmakologie, Frankfurt/M.
PD Dr. Matthias Dollinger and Dr. Jens Walldorf, Universitätsklinik und Poliklinik für Innere Medizin I, Martin-Luther-Universität, Halle
Alexander Zörner, Project Manager Pharmacovigilance, Institut für Klinische Pharmakologie, Medizinische Hochschule Hannover
PhD and Diploma Theses:
M. Graf, Diploma Thesis (Pharmazie) Halle 1999
T. Rogosch, Diploma Thesis (Pharmazie) Halle 2003
T. Rogosch, PhD Thesis Marburg 2005
C. Sinning, PhD Thesis Halle 2008
protoberine-alkaloids
Mainly occurring in plants of the Papaveraceae family, this class of alkaloids is characterised by a tetracyclic ring system which 'hides' a substituted phenethylamine or vanillylamine, depending on viewing 'angle'. The protoberberine alkaloids have (too) many effects, none of them so pronounced that it would be of considerable therapeutic benefit. So far, only a few protoberberines and plant extracts containing them were used medicinally, namely as psychoactive drugs or sedatives. We try to 'extract' and increase effects they have by chemical synthesis of new derivatives and by isolation from plants. In doing this, we thoroughly examined each step required to construct the tetracyclic system, to improve yields, and to explore to the limits and possibilities of ring closures with various substituents. Our protoberberines proved to be very useful in detailed studies of the substrate requirements of CYP isoenzymes, studies undertaken in context of a cooperation with a research group in Finland. CYP are among the most important metabolic enzymes in humans.
Cooperations:
Prof. Dr. Franz Bracher, Department Pharmazie, Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität, München
Prof. Dr. Hannu Raunio, Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio, Finland
PhD and Diploma Theses:
A. Meyer, PhD Thesis Halle 2008
A. Horling, PhD Thesis, Halle 2017