Norlignans from Anemarrhenae asphoeloides Displaying Selective Estrogen Beta (ERβ) Activity

As part of a program to isolate estrogenic compounds from botanicals used in Chinese Medicines, rhizomes of Anemarrhenae asphoeloides (Liliaceae), Chinese name “Zhi Mu”, was subjected to activity-guided isolation to afford a series of norlignans. Anemarrhena has been recorded in the Divine Farmers Materia Medica, the first Chinese pharmacopeia circa 200AD. In Chinese herbal medicine Anemarrhena is commonly used for fever with thirst, dry cough and sensation of dryness like in diabetes. The isolated compounds were assayed for their estrogenic activity using transient transfection assays in the human U2OS bone cell line transiently transfected with either estrogen receptor alpha (ERα) or ERβ and an estrogen response element linked to the luciferase reporter gene (ERE-tkLuc). One of the identified compounds, nyasol is a selective estrogen receptor beta agonist. Nyasol inhibits the growth of MCF-7 breast cancer cells in vitro. It acts as an anti-inflammatory agent by repressing the activation of cytokines such as TNFα and IL-6 via ERβ. Nyasol inhibits breast cancer tumor formation in mouse xenograft models. 2.5 mg of Nyasol in a subcutaneous osmotic pump did not increase uterine weight in mice after 30 days. Given this profile, nyasol may be useful for the treatment of various gynecologic disorders without increasing the risk for cancer seen with natural estrogen.