Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist.
After the Women's Health Initiative found that the risks of hormone therapy outweighed the benefits, a need for alternative drugs to treat menopausal symptoms has emerged. We explored the possibility that botanical agents used in Traditional Chinese Medicine for menopausal symptoms contain ERbeta-selective estrogens. We previously reported that an extract containing 22 herbs, MF101 has ERbeta-selective properties. In this study we isolated liquiritigenin, the most active estrogenic compound from the root of Glycyrrhizae uralensis Fisch, which is one of the plants found in MF101. Liquiritigenin activated multiple ER regulatory elements and native target genes with ERbeta but not ERalpha. The ERbeta-selectivity of liquiritigenin was due to the selective recruitment of the coactivator steroid receptor coactivator-2 to target genes. In a mouse xenograph model, liquiritigenin did not stimulate uterine size or tumorigenesis of MCF-7 breast cancer cells. Our results demonstrate that some plants contain highly selective estrogens for ERbeta.
Mersereau
Jennifer E
JE
Department of Obstetrics, Gynecology and Reproductive Sciences and Center for Reproductive Sciences, Cellular and Molecular Pharmacology, University of California, San Francisco, CA, United States.
Levy
Nitzan
N
Staub
Richard E
RE
Baggett
Scott
S
Zogovic
Tatjana
T
Zogric
Tetjana
T
Chow
Sylvia
S
Ricke
William A
WA
Tagliaferri
Mary
M
Cohen
Isaac
I
Bjeldanes
Leonard F
LF
Leitman
Dale C
DC
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists*; D005260:Female; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014599:Uterus / Q000166:cytology / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D044950:Flavanones; D051958:Nuclear Receptor Coactivator 2; D020845:Selective Estrogen Receptor Modulators; C083152:liquiritigenin