Encapsulated urolithin B–methyl-β-cyclodextrin inclusion complex: synthesis, characterization, in vivo pharmacokinetics with hypolipidemic effect

Urolithin B (UB) has significant health benefits, including a hypolipidemic effect, but its poor water solubility limits its bioavailability and pharmacological activities. In order to increase UB's water solubility, we used cyclodextrin complexation to prepare UB–methyl-β-cyclodextrin inclusion complex (UB–M-β-CD). Our result showed that water solubility of UB in inclusion complex was about 0.3 µg/mL, which was increased by 3875 folds than pure UB. In-vivo pharmacokinetic studies showed the enhanced UB content in rat plasma and the improved bioavailability with UB–M-β-CD. In hyperlipidemic hamsters, UB–M-β-CD reduced body weight and organ fat accumulation more effectively than UB alone. Both UB and UB–M-β-CD decreased serum lipid levels except that of high-density lipoprotein cholesterol. Meantime, UB–M-β-CD reversed hepatic bile acid dysregulation better than UB. Further comprehensive analysis revealed that UB–M-β-CD had the superior effects on hyperlipidemia, suggesting that cyclodextrin complexation enhances the therapeutic potential of UB in modulating liver lipid metabolism. Our results indicate that UB–M-β-CD has the great potentials in treatment of hyperlipidemia and related metabolic disorders.