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

• UB–M-β-CD inclusion complex was easily prepared by the stirring method. • UB–M-β-CD enhanced UB's aqueous solubility by 3875 folds, its in-vivo content and pharmacological efficacy. • UB–M-β-CD more effectively reduced serum lipid levels and organ fat accumulation induced by HFD. • UB–M-β-CD reversed HFD-induced hepatic bile acid levels towards a healthier state. • UB–M-β-CD showed much better hypolipidemic effects than UB alone. 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.