Apigenin acts as a partial agonist action at estrogen receptors in vivo.

The flavone apigenin is widely distributed in vegetables and fruits and has a variety of pharmacological effects. However, there is no definitive scientific evidence that apigenin could act as a phytoestrogen and exert exerting estrogenic or antiestrogenic efficacy in vivo. Therefore, this study was established an ovariectomy (OVX) and estrogenized mouse model to evaluate the effects of apigenin on reproductive target tissues. Our data demonstrated that apigenin could exert a double-directional adjusting estrogenic effect in vivo. Specifically, treatment with apigenin reversed the weight changes caused by abnormal estrogen levels and altered the status of vaginal epithelial cells via the estrogen receptors. In addition, we found that apigenin exhibited a significant estrogenic activity, as indicated by the reversal of uterine atrophy. Apigenin treatment could also regulate the target tissue coefficient changes and estrogen disorders caused by excessive estrogen. Importantly, the administration of apigenin could upregulated the estrogen receptor (ER) α and ER β expression as a partial agonist. Our results demonstrate that apigenin has a double directional adjusting function in different physiological environments.