Available online 30 December 2022

Icaritin soft capsules have been approved for the treatment of advanced HCC.

Structure-activity relationship of flavonoid is elaborated.

Enormous potential of enzymatic hydrolysis in flavonoid preparation is described.

Nanotechnology for overcoming biological barriers and achieving target delivery is summarized.

Integration of herbal medicine, enzyme engineering, and nanotechnology to improve therapeutic effects of flavonoids is first highlighted.

Flavonoids such as baohuoside I and icaritin, are the major active compounds in Epimedii Folium (EF) and possess excellent therapeutic effects on various diseases. Encouragingly, in 2022, icaritin soft capsules have been approved to reach market for the treatment of hepatocellular carcinoma (HCC) by National Medical Products Administration (NMPA) of China. Moreover, recent studies demonstrated that icaritin could be served as immune-modulating agent to exert anti-tumor effects. Nonetheless, both production efficiency and clinical applications of epimedium flavonoids have been restrained because of their low content, poor bioavailability and unfavorable in vivo delivery efficiency. Recently, various strategies including enzyme engineering and nanotechnology, have been developed to increase productivity and activity, improve delivery efficiency, and enhance therapeutic effects of epimedium flavonoids. In this review, the structure-activity relationship of epimedium flavonoids was described. Then, enzymatic engineering strategies for increasing the productivity of highly active baohuoside I and icaritin were discussed. The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases were summarized. Finally, the challenges and an outlook on clinical translation of epimedium flavonoids were proposed.

Flavonoids

Enzymatic hydrolysis

Nanomedicine

Therapeutic effects

Clinical translation

© 2022 The Author(s). Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.