Opioidergic mechanisms underlying the actions of Vitex agnus-castus L.
Vitex agnus-castus (VAC) has been used since ancient Greek times and has been shown clinically to be effective for the treatment of pre-menstrual syndrome. However, its mechanism of action has only been partially determined. Compounds, fractions, and extracts isolated from VAC were used in this study to thoroughly investigate possible opioidergic activity. First, an extract of VAC was found to bind and activate μ- and δ-, but not κ-opioid receptor subtypes (MOR, DOR, and KOR respectively). The extract was then resuspended in 10% methanol and partitioned sequentially with petroleum ether, CHCl(3), and EtOAc to form four fractions including a water fraction. The highest affinity for MOR was concentrated in the CHCl(3) fraction, whereas the highest affinity for DOR was found in the CHCl(3) and EtOAc fractions. The petroleum ether fraction had the highest agonist activity at MOR and DOR. Several flavonoids from VAC were found to bind to both MOR and DOR in a dose-dependent manner; however only casticin, a marker compound for genus Vitex, was found to have agonist activity selective for DOR at high concentrations. These results suggest VAC may exert its therapeutic effects through the activation of MOR, DOR, but not KOR.
Webster
Donna E
DE
UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, University of Illinois, Chicago, IL 60612, USA.
He
Ying
Y
Chen
Shao-Nong
SN
Pauli
Guido F
GF
Farnsworth
Norman R
NR
Wang
Zaijie Jim
ZJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008967:Molecular Biology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011957:Receptors, Opioid / Q000378:metabolism*; D020950:Vitex / Q000737:chemistry*
D004224:Diterpenes; D005419:Flavonoids; D005960:Glucosides; D010936:Plant Extracts; D011957:Receptors, Opioid; C054133:casticin; C452960:agnuside