Prenylflavonoid icariin induces estrogen response element–independent estrogenic responses in a tissue-selective manner

Liping Zhou, Christina Chui Wa Poon, Ka Ying Wong, Sisi Cao, Wenxuan Yu, Xiaoli Dong, Wayne Yuk Wai Lee, Yan Zhang, Man Sau Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

12 Citations (Scopus)


Icariin, a flavonoid phytoestrogen derived from Herba epimedii, has been reported to exert estrogenic effects in bone and activate phosphorylation of estrogen receptor (ER) α in osteoblastic cells. However, it is unclear whether icariin selectively exerts estrogenic activities in bone without inducing undesirable effects in other estrogen-sensitive tissues. The present study aimed to investigate the tissue-selective estrogenic activities of icariin in estrogen-sensitive tissues in vivo and in vitro. Long-term treatment with icariin effectively prevented bone of ovariectomized (OVX) rats from estrogen deficiency–induced osteoporotic changes in bone structure, bone mineral density, and trabecular properties. Moreover, icariin regulated the transcriptional events of estrogen-responsive genes related to bone remodeling and prevented dopaminergic neurons against OVX-induced changes by rescuing expression of estrogen-regulated tyrosine hydroxylase and dopamine transporter in the striatum. Unlike estrogen, icariin did not induce estrogenic effects in the uterus and breast in mature OVX rats or immature CD-1 mice. In vitro studies demonstrated that icariin exerted estrogen-like activities and regulated the expression of estrogen-responsive genes but did not induce estrogen response element–dependent luciferase activities in ER-positive cells. Our results support the hypothesis that icariin, through its distinct mechanism of actions in activating ER, selectively exerts estrogenic activities in different tissues and cell types.

Original languageEnglish
JournalJournal of the Endocrine Society
Issue number2
Publication statusPublished - 1 Feb 2020


  • Estrogen deficiency
  • Estrogen receptor
  • Estrogenic activity
  • Icariin
  • Phytoestrogens
  • Tissue-selectivity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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