Molecular mechanisms of Vitex agnus-castus L. in PMS

Summary

Principal Investigator: Zaijie J Wang
Abstract: Vitex agnus-castus L. (VAC) fruit extracts have been used since ancient times for the relief of premenstrual syndrome (PMS). Recent studies suggest that activation of dopamine D2 receptors and inhibition of prolactin release may account for part of the effect. Evidence also exists for the action through opiate receptors. PMS has been linked to alterations in endogenous opiate peptides. Levels of these peptides fluctuate during menstrual cycles, falling to the lowest in the late-luteal phase when estrogen is at its lowest level. When compared with symptom free subjects, women with PMS show an earlier and larger decrease in opiate peptide levels. In fact, some believe this sharp decrease in opiate levels may cause a mild opiate-withdrawal syndrome seen in PMS, including headache, mood swings, and water retention. High doses of naloxone, a nonselective opiate antagonist, can produce PMS-like symptoms in healthy volunteers. Opiates produce a tonic inhibition on the hypothalamus-pituitary-adrenal axis, thus affecting levels of various hormones. Opiate activity can relieve back and breast pain and mood swings seen in PMS. Activity at the Kappa receptor may help to lessen water retention. In this application, we propose to test the hypothesis that Vitex agnus-castus L. alleviates symptoms of PMS in part through its agonistic actions at the opiate receptors. To test this hypothesis, we will first evaluate the affinity of different VAC extracts for opiate receptors. The extracts will be further tested for their activation of opiate receptors by measuring G protein activation and adenylyl cyclase inhibition. Lastly, to address the effect of these extracts at endogenous opiate receptors, we will evaluate extracts' binding and activation of brain opiate receptors, and behavioral consequence in mice. Data from the current study will help to improve or develop novel therapies for the treatment of PMS.
Funding Period: 2004-09-15 - 2007-07-31
more information: NIH RePORT

Top Publications

  1. pmc Opioidergic mechanisms underlying the actions of Vitex agnus-castus L
    Donna E Webster
    UIC NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, University of Illinois, Chicago, IL 60612, USA
    Biochem Pharmacol 81:170-7. 2011
  2. ncbi Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS
    D E Webster
    Department of Biopharmaceutical Sciences, College of Pharmacy, 833 South Woods Street, Room 335, University of Illinois, Chicago, IL 60612, USA
    J Ethnopharmacol 106:216-21. 2006
  3. pmc Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human mu opiate receptor
    Mee Ra Rhyu
    Department of Medicinal Chemistry and Pharmacognosy, UIC NIH Center for Botanical Dietary Supplements Research and Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois, Chicago, Illinois 60612, USA
    J Agric Food Chem 54:9852-7. 2006

Detail Information

Publications3

  1. pmc Opioidergic mechanisms underlying the actions of Vitex agnus-castus L
    Donna E Webster
    UIC NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, University of Illinois, Chicago, IL 60612, USA
    Biochem Pharmacol 81:170-7. 2011
    ..These results suggest VAC may exert its therapeutic effects through the activation of MOR, DOR, but not KOR...
  2. ncbi Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS
    D E Webster
    Department of Biopharmaceutical Sciences, College of Pharmacy, 833 South Woods Street, Room 335, University of Illinois, Chicago, IL 60612, USA
    J Ethnopharmacol 106:216-21. 2006
    ..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...
  3. pmc Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human mu opiate receptor
    Mee Ra Rhyu
    Department of Medicinal Chemistry and Pharmacognosy, UIC NIH Center for Botanical Dietary Supplements Research and Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois, Chicago, Illinois 60612, USA
    J Agric Food Chem 54:9852-7. 2006
    ..8 +/- 7.7 microg/mL. These results demonstrate for the first time that black cohosh contains active principle(s) that activate hMOR, supporting its beneficial role in alleviating menopausal symptoms...