title: Estrogenic plant extracts reverse weight gain and fat accumulation without causing mammary gland or uterine proliferation.
abstract: Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women.
authors.affiliation: Bionovo Inc., Emeryville, California, United States of America.
authors.forename: Elise F
authors.initials: EF
authors.lastname: Saunier
authors.forename: Omar I
authors.initials: OI
authors.lastname: Vivar
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubenstein
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Zhao
authors.forename: Moshe
authors.initials: M
authors.lastname: Olshansky
authors.forename: Scott
authors.initials: S
authors.lastname: Baggett
authors.forename: Richard E
authors.initials: RE
authors.lastname: Staub
authors.forename: Mary
authors.initials: M
authors.lastname: Tagliaferri
authors.forename: Isaac
authors.initials: I
authors.lastname: Cohen
authors.forename: Terence P
authors.initials: TP
authors.lastname: Speed
authors.forename: John D
authors.initials: JD
authors.lastname: Baxter
authors.forename: Dale C
authors.initials: DC
authors.lastname: Leitman
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D001835:Body Weight; D001940:Breast / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D029882:Glycyrrhiza uralensis / Q000378:metabolism*; D006801:Humans; D008321:Mammary Glands, Animal / Q000187:drug effects*; D051379:Mice; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000378:metabolism*; D029908:Pueraria / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D010936:Plant Extracts