Sophoricoside is a selective LXRβ antagonist with potent therapeutic effects on hepatic steatosis of mice

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the accumulation of triglycerides and associated with obesity, hyperlipidemia and insulin resistance. Currently, there is no therapy for NAFLD. Emerging evidences suggest that the inhibition of liver X receptor (LXR) activity may be a potential therapy for hepatic steatosis. Here, we identified that sophoricoside is a selective antagonist of LXRβ. Sophoricoside protected against obesity and glucose tolerance, and inhibited lipid accumulation in the liver of high-fat diet-induced obesity (DIO) mice and methionine and choline-deficient diet-induced nonalcoholic steatohepatitis mice. Furthermore, sophoricoside inhibited malondialdehyde, and increased superoxide dismutase and glutathione in the liver of the mice. In HepG2 cells, pretreatment with sophoricoside rescued GSH concentration decrease induced by H₂ O₂ treatment. Our data suggest that sophoricoside is a novel LXRβ selective antagonist and may improve glucose and lipid dysfunction, and attenuate lipid accumulation in the liver of DIO mice via anti-oxidant properties, which may be developed as a therapy for NAFLD.

Keywords: LXRβ; antagonist; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; sophoricoside.