Impact of molecular interactions between hydrophilic phytosterol glycosyl derivatives and bile salts on the micellar solubility of cholesterol

Abstract

Hydrophilic phytosterol glycosyl derivatives are synthetic phytosterol analogues by coupling with the glycosyl moiety to improve the water solubility and bioaccessibility of free phytosterols. The aim of this study is to clarify the molecular interaction of phytosterol glycosyl derivatives with bile salts and the consequent impact on cholesterol solubilization. Sharp nonlinear decrease in the micellar solubility of cholesterol and accompanying changes in particle size, zeta potential and microtopography of mixed micelles were observed when phytosterol glycosyl derivatives were introduced in cholesterol-loaded bile salt micelles. These results suggested that β-sitosterol glycosyl derivatives molecules indeed participated in the formation of mixed micelles. Further, nuclear magnetic resonance showed that the structural change of mixed micelles was caused by the insertion of β-sitosterol glycosyl derivatives via hydrogen bonds with sodium taurocholate, which resulted in the low cholesterol solubilization. Moreover, the hydrogen-bond interactions were apparently influenced by the glycosyl moiety of β-sitosterol glycosyl derivatives. These molecular mechanisms may contribute to the development of cholesterol-absorption inhibitors.