Molecular and pharmacodynamic properties of estrogenic extracts from the traditional Chinese medicinal herb, Epimedium.
The Chinese medicinal herb, Epimedium, used traditionally for bone health exerts estrogenic activity (EA) in vitro. A genetically characterized Epimedium brevicornum (EB) extract induced biphasic responses in the mRNA and protein expression of the estrogen-regulated progesterone receptor gene in breast cancer (MCF-7) cells. These changes were mirrored changes in estrogenic receptor (ERalpha) content. In male Sprague-Dawley rats, administration of the estrogenic prodrug, estradiol valerate increased area-under-curve of serum effects for ERalpha (AUC difference: 18,900EA(ERalpha) min; 95% CI: 0-37,800; p = 0.05) and breast cancer cell (MCF-7) growth (AUC difference: 30,200EA(MCF-7) min; 95% CI: 24,200-36,200; p<0.001), compared to placebo. Oral administration of Epimedium brevicornum increased ERalpha activity (1320EA(ERalpha) min, p<0.01). Our data indicate that estrogen-responsive bioassays can measure the pharmacokinetic/pharmacodynamics of estrogenic activity in serum. Epimedium brevicornum extract increases estrogenic activity in serum and human studies are required to evaluate whether Epimedium extracts have utility for estrogen replacement therapy.
Yap
S P
SP
Department of Obstetrics & Gynecology, National University Hospital, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Shen
P
P
Li
J
J
Lee
L S
LS
Yong
E L
EL
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D034181:Epimedium / Q000737:chemistry*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D048789:Phytoestrogens / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology
D002352:Carrier Proteins; D004365:Drugs, Chinese Herbal; D047628:Estrogen Receptor alpha; D048789:Phytoestrogens; D010936:Plant Extracts; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C010140:estrophilin; D013629:Tamoxifen; D004958:Estradiol