Binding mechanism of Lentinus edodes ergosterol with HP-β-CD: Insights from in silico simulations

To enhance the solubility and stability of Lentinus edodes ergosterol, this study was designed to investigate the potential of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to form a stable inclusion complex (IC) with ergosterol. Using signal factor and Box-Behnken design, the maximum encapsulation efficiency of 86.4 ± 0.4 % was achieved at a 1:10.5 core-shell ratio, 400 rpm stirring speed, and 32 h stirring time. The IC showed superior stability under light and heat conditions. It had higher bioaccessibility, antioxidant activity and cholesterol reduction compared to free ergosterol. Molecular docking, dynamics simulations, and multispectral analysis revealed that electrostatic, hydrophobic, H-bonds, and van der Waals interactions drove the inclusion mechanism, and the IC transformed ergosterol's crystal form into an amorphous structure, enhancing its water solubility to 66.7 ± 1.7 μg/mL. This study confirms that the IC with HP-β-CD can enhance the properties of ergosterol, offering a promising method to improve its effective delivery.