Modification of taxifolin particles with an enteric coating material promotes repair of acute liver injury in mice through modulation of inflammation and autophagy signaling pathway.

Abstract

Taxifolin (TAX) is a flavanol compound with hepatoprotective effect, but its application is severely limited by its poor water solubility and low oral bioavailability. Therefore, it is important to urgently find a method to improve the oral bioavailability of TAX. In this study, hydroxypropyl methylcellulose acetate succinate modified taxifolin liposomes (HPMCAS-TAX-Lips) were prepared by a thin-film dispersion method, and a series of physicochemical properties of the liposomes were studied. The cumulative in vitro release rates of free TAX, taxifolin liposomes (TAX-Lips), and HPMCAS-TAX-Lips in the simulated gastrointestinal fluid were measured by in vitro release experiments, and the effect of HPMCAS-TAX-Lips on the human hepatoellular carcinomas (HepG2) cells was detected by MTT assay. Finally, the hepatoprotective mechanism of HPMCAS-TAX-Lips was explored through in vivo experiments. The results showed that the particle size of HPMCAS-TAX-Lips was 100.44±2.85nm, the zeta potential was -51.13±0.57mV, the PDI was 0.170±0.088, and the EE was 87.9±3.73%. The in vitro release results showed that the cumulative release rates of TAX-Lips and HPMCAS-TAX-Lips in simulated gastric fluid for 24h were 92.60±5.31% and 66.91±1.20%, respectively. The cumulative release rates in simulated intestinal fluid for 24h were 72.61±4.38% and 53.94±3.2%, respectively. The results of cytotoxicity experiments proved that HPMCAS-TAX-Lips had a significant inhibitory effect on HepG2 cells. In vivo experiments further showed that HPMCAS-TAX-Lips significantly improved the survival rate of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury mice and exerted hepatoprotective effects by regulating the expression of autophagy proteins and inhibiting the activation of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. This study proved the significant hepatoprotective effect of HMPCAS-TAX-Lips and provided a new idea for the application of TAX.