Boosting the Solubility and Bioactivity of Flavonoids in Nontoxic Betaine-Based Natural Eutectic Solvents
Por:
Jiménez-Ortega, LA, Juarez-Moreno, K, Quiñonez-Angulo, P, León-Félix, J, Bastidas-Bastidas, PD, Chaidez, C, González-Gómez, JP, Mota-Morales, JD, Heredia, JB
Publicada:
18 ago 2025
Ahead of Print:
1 jul 2025
Resumen:
This study presents a green and efficient method for solubilizing hydrophobic bioactive flavonoids using natural deep eutectic solvents (NaDES), emphasizing the use of the complete NaDES-flavonoid systems for enhanced functionality. Among the investigated NaDES, betaine:glycerol (1:2 molar ratio) with 20 wt % water achieved the highest solubility for quercetin (3.36 mg/mL), rutin (5.95 mg/mL), naringenin (5.82 mg/mL), and naringin (13.32 mg/mL). NaDES-containing flavonoids were structurally characterized using 1H NMR and FTIR spectroscopies and thermally analyzed by DSC, revealing a high thermal stability. The NaDES-quercetin system exhibited not only the highest antioxidant activity but also cooperative and significant antibacterial effects against multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa, achieving 91.3% and 94.8% reduction, respectively. Both the neat NaDES and the flavonoid-containing systems were noncytotoxic to 3T3-L1 fibroblasts and HaCaT keratinocytes at concentrations up to 100 mu g/mL. NADES-containing flavonoids inhibited reactive oxygen species (ROS) production in a time- and dose-dependent manner, while the NADES-quercetin system promoted wound healing in fibroblasts in vitro at lower concentrations. The complete NaDES-flavonoid systems, exemplified by hydrated betaine-glycerol NaDES with quercetin solubility increased by 23,850-fold compared to water, exhibit markedly enhanced bioactivities and hold significant promise for sustainable pharmaceutical applications, based on AGREE and AGREEprep scores.
Filiaciones:
Jiménez-Ortega, LA:
Ctr Invest Alimentac & Desarrollo, Sinaloa 80110, Mexico
Juarez-Moreno, K:
Univ Nacl Autonoma Mexico, Ctr Fis Aplicada & Tecnol Avanzada, Queretaro 76230, Mexico
Quiñonez-Angulo, P:
Univ Nacl Autonoma Mexico, Ctr Fis Aplicada & Tecnol Avanzada, Queretaro 76230, Mexico
Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA
León-Félix, J:
Ctr Invest Alimentac & Desarrollo, Sinaloa 80110, Mexico
Bastidas-Bastidas, PD:
Ctr Invest Alimentac & Desarrollo, Sinaloa 80110, Mexico
Chaidez, C:
Ctr Invest Alimentac & Desarrollo, Sinaloa 80110, Mexico
González-Gómez, JP:
Ctr Invest Alimentac & Desarrollo, Sinaloa 80110, Mexico
Mota-Morales, JD:
Univ Nacl Autonoma Mexico, Ctr Fis Aplicada & Tecnol Avanzada, Queretaro 76230, Mexico
Heredia, JB:
Ctr Invest Alimentac & Desarrollo, Sinaloa 80110, Mexico
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