Irilone from Red Clover (Trifolium pratense) Potentiates Progesterone Signaling

Autor: Jung-Ho Lee, Joanna E. Burdette, Matthew Dean, Julia R Austin, Brian T. Murphy
Rok vydání: 2018
Předmět:
Zdroj: Journal of Natural Products. 81:1962-1967
ISSN: 1520-6025
0163-3864
DOI: 10.1021/acs.jnatprod.8b00131
Popis: The use of botanical dietary supplements is becoming increasingly popular for the alleviation of hormonal-based conditions such as hot flashes, premenstrual syndrome, and fertility. Estrogen and progesterone receptors (ER and PR) play an essential role in these processes. However, despite the fact that many therapies used to alleviate gynecological conditions act through PR-mediated mechanisms, few studies have investigated or identified any herbal natural product components that act on this receptor. In the current study, we used a progesterone response element (PRE)-luciferase (Luc) reporter assay to identify four phytoprogestins present in a standardized red clover extract. While looking for compounds in red clover, a synergistic interaction was identified between progesterone and irilone (1) in both endometrial and ovarian cancer cell lines. In these cancers, progesterone action is generally associated with positive outcomes, thus the synergistic activity of 1 may provide entirely new strategies for enhancing progesterone signaling as a means of mitigating conditions such as fibroids and endometriosis. Formononetin (3) and biochanin A (4) exhibited mixed antagonist activity, while prunetin (2) acted only as an antagonist. Collectively these results suggest that the effects of red clover extract repeatedly observed in cultured cells, and the inverse correlation between risk of various cancers and flavonoid intake may be due, in part, to altered progesterone signaling.
Databáze: OpenAIRE