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 were approved to reach the market for the treatment of hepatocellular carcinoma (HCC) by National Medical Products Administration (NMPA) of China. Moreover, recent studies demonstrate that icaritin can serve 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 is described. Then, enzymatic engineering strategies for increasing the productivity of highly active baohuoside I and icaritin are discussed. The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized. Finally, the challenges and an outlook on clinical translation of epimedium flavonoids are proposed.

In this study, a novel strategy was established to produce diosgenin from Discorea nipponica Makino tubers, in which pressurized biphase acid hydrolysis and Soxhlet extraction of total saponins were incorporated for the first time. The hydrolysis conditions were optimized by response surface methodology after the preliminary investigation on affecting factors by single-factor experiments and L₁₆(4⁵) orthogonal experiments. Under the optimal conditions, namely dioscin (eq. 8 g of the DNM tubers) was hydrolyzed in a biphase system composed of 50 mL of 6 μL/mL H₂SO₄ solution and 50 mL of petroleum ether (90–120°C) at 140°C for 2 h, the highest yield of diosgenin has been achieved at 1.87%, that was 85.1% higher than the conventional method while the H₂SO₄ consumption reduced by 92.5%. The results demonstrated that the newly developed approach was more effective and cleaner, and promising value-added technology for the extraction of diosgenin from DNM tubers in industrial application. GRAPHICAL ABSTRACT