Estrogen Receptor (ER) Subtype Selectivity Identifies 8-Prenylapigenin as an ER? Agonist from Glycyrrhiza inflata and Highlights the Importance of Chemical and Biological Authentication.

ABSTRACT: Postmenopausal women are increasingly using botanicals for menopausal symptom relief due to the increased breast cancer risk associated with traditional estrogen therapy. The deleterious effects of estrogens are associated with estrogen receptor (ER)?-dependent proliferation, while ER? activation could enhance safety by opposing ER? effects. Three medicinal licorice species, Glycyrrhiza glabra ( G. glabra), G. uralensis, and G. inflata, were studied for their differential estrogenic efficacy. The data showed higher estrogenic potency for G. inflata in an alkaline phosphatase induction assay in Ishikawa cells (ER?) and an estrogen responsive element (ERE)-luciferase assay in MDA-MB-231/?41 breast cancer cells (ER?). Bioassay-guided fractionation of G. inflata led to the isolation of 8-prenylapigenin (3). Surprisingly, a commercial batch of 3 was devoid of estrogenic activity. Quality control by MS and qNMR revealed an incorrect compound, 4'- O-methylbroussochalcone B (10), illustrating the importance of both structural and purity verification prior to any biological investigations. Authentic and pure 3 displayed 14-fold preferential ER? agonist activity. Quantitative analyses revealed that 3 was 33 times more concentrated in G. inflata compared to the other medicinal licorice extracts. These data suggest that standardization of G. inflata to 3 might enhance the safety and efficacy of G. inflata supplements used for postmenopausal women's health.

SUBMITTER: Hajirahimkhan A 

PROVIDER: S-EPMC5928484 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature