Highly efficient and selective extraction of minor bioactive natural products using pure ionic liquids: Application to prenylated flavonoids in licorice

Lots of minor constituents in herbal medicines have shown great potential to devolve into lead compounds, and their extraction is attracting more and more attention in pharmaceutical industry. This study provided an example that showed efficient and selective extraction of minor bioactive natural products (prenylated flavonoids with anti-cancer activities) from an herbal medicine (licorice) using pure ionic liquids as green solvents. After investigation of a variety of hydrophobic ionic liquids with ultrasonic-assisted extraction, we found that [C8MIM]BF4 (1-octyl-3-methylimidazolium tetrafluoroborate) was the most effective one for extraction of five representative compounds (isoangustone A, glycycoumarin, licoisoflavanone, licoricidin and glabridin), and solvent to solid ratio, extraction time, extraction temperature and soaking time were then optimized through single-factor experiments and response surface methodology. As a result, the established method had significantly higher extraction selectivity than conventional organic solvents, which could be attributed to significant physical change of licorice microstructures after extraction, as well as strong interactions (especially hydrogen bond interactions) between [C8MIM]BF4 and prenylated flavonoids by mechanism study. In addition, 78.92% of the extracted prenylated flavonoids could be readily recovered from [C8MIM]BF4 by using reversed-phase solid phase extraction, and the recyclability of [C8MIM]BF4 was also confirmed.