The Chrysin Solid Dispersion Prepared Using Polyvinylpyrrolidone K40 Demonstrates Enhanced Solubility and a Thermogenesis-Promoting Effect on adipocytes

Chrysin, a natural flavonoid compound found in honey, propolis, and various plant sources, was reported to promote adipocyte thermogenesis and improve metabolism in obese mice. However, its clinical application is hindered by poor water solubility and low bioavailability. In this study, water-soluble chrysin solid dispersions were prepared using polyvinylpyrrolidone (K10, K40, K90), polyethylene glycol (1000, 2000, 6000), and maltitol. Among these, polyvinylpyrrolidone K40 (PVPK40) was identified as the optimal carrier for preparing PVPK40-chrysin solid dispersion (PVPK40-Chy SD), achieving a 1200-fold higher aqueous solubility than crystalline chrysin. The PVPK40-Chy SD exhibited a more soluble amorphous structure compared to crystalline chrysin. Hydrogen bonding interactions were observed between chrysin and the carrier. Additionally, an in vitro digestion model confirmed the improved dissolution behavior of chrysin. Finally, in vivo and in vitro experiments have demonstrated that the water-soluble chrysin solution, which was formed by dissolving PVPK40-Chy SD in water, can effectively promote adipocyte thermogenesis in C3H10T1/2 cells and mice. The mean UCP1 protein level in the water-soluble chrysin-treated group reached 2.02-fold that of the control group, thereby stimulating adipocyte thermogenesis. Following 2 h of cold exposure, mice in the water-soluble chrysin-treated group exhibited a mean rectal temperature 3.2 °C higher than animals in the PVPK40 carrier group, indicating remarkably enhanced cold tolerance.