Encapsulation of hyperoside with acyclic cucurbiturils: Supramolecular binding behavior, water solubility and in vitro antioxidant activity

Hyperoside (Hyp) is a natural flavonol glycoside widely present in plants, which possesses important pharmacological activities including anti-inflammatory, anti-viral, organ-protection, antioxidant, and anti-tumor, etc. However, its poor water solubility and low oral bioavailability severely limit its further development for pharmaceutical uses. In this work, solid inclusion complexes of Hyp with two acyclic cucurbiturils (ACBs, M1 and M2) were prepared by the method of suspension. The formation of inclusion complexes was confirmed by Fourier transform infrared (FT-IR), powder X-ray diffraction (PXRD) and nuclear magnetic resonance (NMR) analyses. Based on Job's plot, proton nuclear magnetic resonance (1H NMR) spectroscopy, two-dimensional diffusion ordered spectroscopy (2D-DOSY), two-dimensional rotating-frame Overhauser enhancement spectroscopy (2D-ROESY) and molecular docking experiments, a 1:1 inclusion mode was rationally proposed. The binding stability constants (Ks) were determined by fluorescence titration, up to 4.22 × 104 and 6.97 × 104 L·mol-1 for Hyp/M1 and Hyp/M2, respectively. After inclusion complexation with ACDs, the water solubility of Hyp was elevated by more than 300-fold, which was much superior to that with cyclodextrins. Furthermore, in vitro antioxidant activity of Hyp was significantly promoted by formation of inclusion complexes. These results would inspire new strategies for further developments of Hyp for pharmaceutical uses.