Prenylated flavonoids icariin and icaritin for drug discovery: structural modifications and bioactivity studies

Prenylated flavonoids icariin and icaritin are the crucial ingredients of traditional Chinese medicinal Herb Epimedii. Icariin is an isoprenoid flavonoid glycoside, and icaritin is the aglycon of icariin. During the past decades, icariin and icaritin have generated a lot of interest in the biological and clinic applications, and icaritin has been an approved drug for advanced HCC in China in 2022. However, poor water solubility, low therapeutic efficiency and poor pharmacokinetic properties are the major obstacles, which had significantly limited their clinical application. Given the pivotal role of icariin and icaritin, this review comprehensively reviews the structural modifications of icariin and icaritin, which might help to provide novel insights for the development of novel derivatives of icariin and icaritin with favorable pharmacological profiles and promising clinical application potential.