Biological characterization of non-steroidal progestins from botanicals used for women鈥檚 health
- 作者：M.F. Toh ; J. Sohn ; S.N. Chen ; P. Yao ; J.L. Bolton ; J.E. Burdette ; joannab@uic.edu
- 关键词：Progesterone receptor ; Red clover ; Flavonoid ; Kaempferol ; Apigenin ; Naringenin
- 刊名：Steroids
- 出版年：2012
- 期刊代码：142_0039128x
- 类别：bio
- 出版时间：June, 2012
- 卷：77
- 期：7
- 页码：765-773
- 文件大小：680 K
摘要
Progesterone plays a central role in women鈥檚 reproductive health. Synthetic progestins, such as medroxyprogesterone acetate (MPA) are often used in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Although MPA is clinically effective, it also promiscuously binds to androgen and glucocorticoid receptors (AR/GR) leading to many undesirable side effects including cardiovascular diseases and breast cancers. Therefore, identifying alternative progestins is clinically significant. The purpose of this study was to biologically characterize non-steroidal progestins from botanicals by investigating their interaction and activation of progesterone receptor (PR). Eight botanicals commonly used to alleviate menopausal symptoms were investigated to determine if they contain progestins using a progesterone responsive element (PRE) luciferase reporter assay and a PR polarization competitive binding assay. Red clover extract stimulated PRE-luciferase and bound to PR. A library of purified compounds previously isolated from red clover was screened using the luciferase reporter assay. Kaempferol identified in red clover and a structurally similar flavonoid, apigenin, bound to PR and induced progestegenic activity and P4 regulated genes in breast epithelial cells and human endometrial stromal cells (HESC). Kaempferol and apigenin demonstrated higher progestegenic potency in the HESC compared to breast epithelial cells. Furthermore, phytoprogestins were able to activate P4 signaling in breast epithelial cells without downregulating PR expression. These data suggest that botanical extracts used for women鈥檚 health may contain compounds capable of activating progesterone receptor signaling.