Estrogenic effects of herbal medicines from Costa Rica used for the management of menopausal symptoms.
OBJECTIVE
Outcomes from the Women's Health Initiative have demonstrated adverse effects associated with hormone therapy and have prioritized the need to develop new alternative treatments for the management of menopause and osteoporosis. To this end, we have been investigating natural herbal medicines used by Costa Rican women to manage menopausal symptoms.


METHODS
Seventeen plant species were collected and extracted in Costa Rica. To establish possible mechanisms of action and to determine their potential future use for menopause or osteoporosis, we investigated the estrogenic activities of the herbal extracts in an estrogen-reporter gene estrogen receptor (ER) beta-Chemically Activated Luciferase Expression assay in U2-OS cells and in reporter and endogenous gene assays in MCF-7 cells.


RESULTS
Six of the plant extracts bound to the ERs. Four of the six extracts stimulated reporter gene expression in the ER-beta-Chemically Activated Luciferase Expression assay. All six extracts modulated expression of endogenous genes in MCF-7 cells, with four extracts acting as estrogen agonists and two extracts, Pimenta dioica and Smilax domingensis, acting as partial agonist/antagonists by enhancing estradiol-stimulated pS2 mRNA expression but reducing estradiol-stimulated PR and PTGES mRNA expression. Both P. dioica and S. domingensis induced a 2ERE-luciferase reporter gene in transient transfected MCF-7 cells, which was inhibited by the ER antagonist ICI 182,780.


CONCLUSIONS
This work presents a plausible mechanism of action for many of the herbal medicines used by Costa Rican women to treat menopausal symptoms. However, it further suggests that studies of safety and efficacy are needed before these herbs should be used as alternative therapies to hormone therapy.
Departments of Medicinal Chemistry and Pharmacognosy and Pharmacy Practice, College of Pharmacy, Pan-American Health Organization/World Health Organization Collaborating Centre for Traditional Medicine, Chicago, IL 60612, USA.
Brian J
BJ
Doyle
Jonna
J
Frasor
Lauren E
LE
Bellows
Tracie D
TD
Locklear
Alice
A
Perez
Jorge
J
Gomez-Laurito
Gail B
GB
Mahady
D001667:Binding, Competitive; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D003364:Costa Rica; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008593:Menopause / Q000187:drug effects*; D048789:Phytoestrogens / Q000008:administration & dosage* / Q000009:adverse effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000032:analysis; D011980:Receptors, Progesterone / Q000235:genetics; D014162:Transfection; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D048789:Phytoestrogens; D010936:Plant Extracts; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D000077267:Fulvestrant; D004958:Estradiol; D008156:Luciferases; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases