Lipid peroxide-regulated nanoparticles prevent the progression of nonalcoholic steatohepatitis by reducing lipid deposition and eliminating oxidative-stress

Abstract

Non-alcoholic fatty liver disease (NAFLD) was a pathological syndrome characterized by excessive lipid deposition in the liver. Excessive lipid in the liver produced reactive oxygen species (ROS), the occurrence of oxidative stress and lipid peroxidation was accelerated, which aggravated liver function damage. Based on these, resveratrol, a natural antioxidan, was encapsulated in liposoluble interior by amphiphilic phosphatidylserine, and then self-assembled with chitosan oligosaccharide complexed with zinc ions to form Zn-Cos/Res@Ps nanoparticles. The size of the Zn-Cos/Res@Ps was about 168.57 ± 4.35 nm, and the zeta potential was about 17.45 ± 1.79 mV. Furthermore, Zn-Cos/Res@Ps could significantly inhibition of lipid deposition, decreased the contents of reactive oxygen species (ROS) and synergistically decreased the levels of malondialdehyde (MDA) in HepG2 cells. Zn-Cos/Res@Ps could also reduce the content of serum total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), improved the liver injury and reduced the degree of liver fibrosis in mice. The Zn-Cos/Res@Ps group showed better results than the single-drug nanoparticle group. In conclusion, Zn-Cos/Res@Ps nanoparticles could effectively alleviate the disease progression by inhibiting oxidative stress and lipid peroxidation, promoted fatty acid catabolism, and effectively reverse and prevent the progress of nonalcoholic steatohepatitis.