Solubilization of quercetin by a modified citrus pectin fraction: Structural characterization, molecular interactions, and enhanced antioxidant activity.

Quercetin is a bioactive flavonoid with diverse biological activities, but its poor aqueous solubility limits bioavailability and practical applications. In this study, the acid-modified citrus pectin fraction MCP-2 was used as a natural solubilizing matrix to improve the aqueous solubility of quercetin. Quercetin solubility reached a maximum at 1.0 mg/mL MCP-2, approximately 3.9-fold that in water. Methylation analysis and nuclear magnetic resonance (NMR) spectroscopy indicated that the MCP-2 backbone was mainly composed of galactopyranuronic acid (GalpA), methyl-esterified GalpA, and galactopyranosyl (Galp) residues, with minor rhamnopyranosyl (Rhap) residues and short GalpA-containing side chains attached to Rhap units. X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and molecular dynamics simulations provided consistent evidence for the formation of a stable MCP-2/quercetin complex through noncovalent interactions. Compared with quercetin and the MCP-2/quercetin physical mixture, the MCP-2/quercetin complex exhibited stronger antioxidant activity in chemical radical-scavenging assays and showed improved protection against H2O2-induced oxidative injury in HepG2 cells. Overall, this study elucidates the mechanism of MCP-2-mediated quercetin solubilization and provides a natural polysaccharide-based strategy for improving the aqueous solubility and functional performance of poorly water-soluble flavonoids.