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

This study proved the significant hepatoprotective effect of HMPCAS-TAX-Lips and provided a new idea for the application 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.

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.

The results showed that the particle size of HPMCAS-TAX-Lips was 100.44 ± 2.85 nm, the zeta potential was - 51.13 ± 0.57 mV, 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 24 h were 92.60 ± 5.31% and 66.91 ± 1.20%, respectively. The cumulative release rates in simulated intestinal fluid for 24 h 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.