Analysis of benzodiazepines and ligands of the benzodiazepine receptor in natural matrices
Project management at the University of Würzburg:
Using the combination of radio receptor assay with chromatographic and spectroscopic techniques (HPLC-MS/MS; SRM), in part A of the project the occurrence of benzodiazepines (bzd) in extracts of sterile cultures of Artemisia dracunculus and Solanum tuberosum was demonstrated, rationalizing the endogeneous bzd formation from plant tissues.
With the aim to study bzd receptor (bzd-r) active ligands in plants, after a comprehensive screening of various plant tissues, the attention was focused on sage (Salvia officinalis) (part B). With the flavones apigenine, hispiduline, cirsimaritine and the diterpenes 7-methoxyrosmanol and galdosol five bzd-r active constituents were found. Among them hispiduline and galdosol showed the highest activities (IC50 around 1 Mikromol).
After chemical synthesis of hispiduline it was subjected to further activity studies. In the Xenopus oocyte model it exhibited agonistic activity, however, owing to the binding to the alpha6beta2gamma2 receptor subtype, differing from that of the bzd diazepam. In experiments carried out with the Mongolian gerbil hispiduline showed anticonvulsive properties. Due to these results, additional studies were initiated concerning bioavailability and metabolism of this bioactive flavone.
Projekt period: from 01.1999 to 12.2001
DFG ,Granting date: 01.09.1998