Inclusion effect and structural basis of cyclodextrins for increased extraction of medicinal alkaloids from natural medicines.

The enhancing effects of alpha-, beta-, and gamma-cyclodextrins (CyDs) on the aqueous extraction of ephedrine and berberine from the natural medicines were investigated in HPLC analysis, and the greatest effect was observed for beta- and gamma-CyDs. To clarify the structural basis of such an increased extraction effect with beta-CyD, possible interaction modes of (1R,2S)-ephedrine with alpha-, beta-, and gamma-CyDs were investigated using molecular dynamic simulations in an aqueous solution system. It was shown that the wrapping model of ephedrine by beta-CyD is the most compact and thus increases the solubility most effectively, compared with those by other CyDs. The same mode could be possible for the greatest effect of gamma-CyD on the extraction of berberine from natural medicines. This clearly shows that CyDs are useful additives for the effective extraction of bioactive alkaloids from natural medicines.