Assessment of estrogenic activity in some common essential oil constituents.
Estrogenic responses have not only been associated with endocrine function, but also with cognitive function. Several studies have indicated that estrogen replacement therapy has favourable effects on cognition, and may have potential in the prevention and treatment of Alzheimer's disease. Thus, ligands for the estrogen receptor, that have a better efficacy and adverse-effect profile than drugs currently available, require investigation. This study was undertaken to investigate the potential estrogenic activity of a number of essential oil constituents. Initially, estrogenic activity was determined by a sensitive and specific bioassay using recombinant yeast cells expressing the human estrogen receptor. At high concentrations, estrogenic activity was detected for citral (geranial and neral), geraniol, nerol and trans-anethole, while eugenol showed anti-estrogenic activity. Molecular graphics studies were undertaken to identify the possible mechanisms for the interaction of geranial, neral, geraniol, nerol and eugenol with the ligand-binding domain of the estrogen alpha-receptor, using the computer program HyperChem. Citral, geraniol, nerol and eugenol were also able to displace [(3)H]17beta-estradiol from isolated alpha- and beta-human estrogen receptors, but none of these compounds showed estrogenic or anti-estrogenic activity in the estrogen-responsive human cell line Ishikawa Var I at levels below their cytotoxic concentrations, and none showed activity in a yeast screen for androgenic and anti-androgenic activity. The potential in-vivo estrogenic effects of citral and geraniol were examined in ovariectomized mice, but neither compound showed any ability to stimulate the characteristic estrogenic responses of uterine hypertrophy or acute increase in uterine vascular permeability. These results show that very high concentrations of some commonly used essential oil constituents appear to have the potential to interact with estrogen receptors, although the biological significance of this is uncertain.
Howes
M-J R
MJ
Department of Pharmacy, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 8WA, UK.
Houghton
P J
PJ
Barlow
D J
DJ
Pocock
V J
VJ
Milligan
S R
SR
D000279:Administration, Cutaneous; D000818:Animals; D001667:Binding, Competitive; D002199:Capillary Permeability / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009822:Oils, Volatile / Q000737:chemistry*; D009929:Organ Size; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D008024:Ligands; D009822:Oils, Volatile; D011960:Receptors, Estrogen