Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS.
The dried ripe fruit of Vitex agnus-castus L. (VAC) is widely used for the treatment of premenstrual syndrome (PMS). A previous study reported that extracts of VAC showed affinity to opiate receptors; however, functional activity was not determined. We tested two different VAC extracts in receptor binding and functional assays. Our objectives were: (1) to confirm the opiate affinity; (2) to rule out interference by free fatty acids (FFA); (3) to determine the mode of action of VAC at the mu-opiate receptor. Methanol extracts of VAC were prepared either before (VAC-M1) or after (VAC-M2) extraction with petroleum ether to remove fatty acids. Both extracts showed significant affinities to the mu-opiate receptor, as indicated by the concentration-dependent displacement of [3H]DAMGO binding in Chinese hamster ovary (CHO)-human mu-opiate receptor (hMOR) cells. The IC50 values were estimated to be 159.8 microg/ml (VAC-M1) and 69.5 microg/ml (VAC-M2). Since the defatted extract not only retained, but exhibited a higher affinity (p<0.001), it argued against significant interference by fatty acids. In an assay to determine receptor activation, VAC-M1 and VAC-M2 stimulated [35S]GTPgammaS binding by 41 and 61% (p<0.001), respectively. These results suggested for the first time that VAC acted as an agonist at the mu-opiate receptor, supporting its beneficial action in PMS.
Webster
D E
DE
Department of Biopharmaceutical Sciences, College of Pharmacy, 833 South Woods Street, Room 335, University of Illinois, Chicago, IL 60612, USA.
Lu
J
J
Chen
S-N
SN
Farnsworth
N R
NR
Wang
Z Jim
ZJ
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005638:Fruit; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D000432:Methanol; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011293:Premenstrual Syndrome / Q000188:drug therapy / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012997:Solvents; D014162:Transfection; D020950:Vitex
D010936:Plant Extracts; D017450:Receptors, Opioid, mu; D012997:Solvents; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000432:Methanol