Abstract
Introduction
Extracts of Vitex agnus-castus (VAC) are used for the treatment of premenstrual symptoms. The mechanism of action
was proposed to be dopaminergic and estrogenic in nature. To isolate these endocrinologically
active substances, receptor ligand binding assays and cell cultures were used as in vitro systems to monitor the bioactivity-guided chromatographic separation.
Methods
Estrogen receptor (ER) and Dopamine D2-receptor ligand binding assays were performed with human recombinant receptor protein.
Both known ERs (ERα and ERβ) were used. Cultures of anterior pituitary cells were
prepared from 3 months old female rats. The concentrations of prolactin (PRL) and
of cAMP in the supernatants were measured by radio immunoassay (RIA). Starting material
for the isolation of single constituents was the aqueous ethanol 70% (v/v) VAC extract
BNO 1095. The fractionations were performed with high speed counter current or Sephadex-LH-20
chromatography. Structure elucidation was conducted with GC–MS, LC–MS, 1H NMR and 13C NMR.
Results
The bio-guided fractionation of BNO 1095 resulted in the isolation of dopaminergic
bicyclic diterpenes. The fraction with the highest dopaminergic activity was a mixture
of diterpenes of the clerodane type, designated as “BNO-diterpenes”. These newly isolated
diterpenes inhibited cAMP formation and PRL-release in rat pituitary cell cultures.
The estrogenic compounds in BNO 1095 were identified as the flavonoids penduletin
and apigenin. Both substances are specific ligands for the ERβ.
Conclusion
Using the strategy of bioactivity-guided fractionation we were able to isolate new
dopaminergic diterpenes with a high specific activity which contribute significantly
to the PRL-lowering activity of VAC. The therapeutical potential of the ERβ specific
ligands penduletin and apigenin needs further investigation.
Keywords
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Article info
Publication history
Published online: July 20, 2006
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
