Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS

J Ethnopharmacol. 2006 Jun 30;106(2):216-21. doi: 10.1016/j.jep.2005.12.025. Epub 2006 Jan 24.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cricetinae
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / metabolism
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Female
  • Fruit
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Methanol
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Premenstrual Syndrome / drug therapy
  • Premenstrual Syndrome / metabolism
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism
  • Solvents
  • Transfection
  • Vitex*


  • Plant Extracts
  • Receptors, Opioid, mu
  • Solvents
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Methanol