The challenge of flavonoid/cyclodextrin complexation in a complex matrix of the quercetin, luteolin, and 3-O-methylquercetin

The complexation of herbal constituents with cyclodextrin has been a useful tool to improve their aqueous solubility. However, the simultaneous complexation of these compounds still lacks detailed studies. The present study investigated the multicomplexation of quercetin (QCT), luteolin (LUT), and 3-O-methylquercetin (3OMQ) with (2-hydroxypropyl)-β-cyclodextrin (HPβCD), when they are simultaneously contained in a flavonoid-enriched fraction (FEF) of Achyrocline satureioides. The phase-solubility diagram revealed a linear correlation between the flavonoids solubility and the HPβCD concentration, demonstrating the formation of complexes with a 1:1 stoichiometric ratio, which was confirmed by ESI-MS. Negative ΔG0 values indicated that complexation was spontaneous. Flavonoids/HPβCD interactions were evidenced by FT-IR, DSC, SEM, and 1D and 2D NMR. The last one showed the formation of inclusion complexes by insertion of the B-ring of the flavonoids into the cavity of HPβCD. Unexpectedly, the FEF/HPβCD complex showed a radical scavenger potential lower than the FEF. The HPLC analysis revealed that the complex contained different flavonoid ratio than the fraction. Thus, the antioxidant capacity of the samples was demonstrated to be related to the ratio among the flavonoids, rather than to the total flavonoids. These new findings are very useful for developing herbal cyclodextrin-based products from A. satureioides or other herbal products.