Osthole attenuates lipid accumulation, regulates the expression of inflammatory mediators, and increases antioxidants in FL83B cells.

Abstract

Osthole is found in Cnidium monnieri (L.) and has anti-inflammatory and anti-oxidative properties. It also inhibits the proliferation of hepatocellular carcinoma cells. This study aimed to evaluate the osthole suppressive nonalcoholic fatty liver disease effects in oleic acid (OA)-induced hepatic steatosis and if it can modulate inflammatory responses and oxidative stress. FL83B cells were pretreated with OA (250μΜ) for 24h, and then added different concentrations of osthole (3-100μM) for 24h. Subsequently, lipolysis and transcription factors of adipogenesis and phosphorylation of AMP-activated protein kinase proteins were measured. In addition, cells with OA-induced steatosis were H2O2-stimulated, and then incubated with osthole to evaluated if it could suppress its progression to steatohepatitis. Osthole significantly enhanced glycerol release and lipolysis protein expression. Osthole also promoted phosphorylation of AMP-activated protein kinases and increased the activity of triglyceride lipase and hormone- sensitive lipase. Osthole suppressed the nuclear transcription factor kappa-B and the p38 mitogen-activated protein kinase pathway, and decreased the malondialdehyde concentration in FL83B cells with OA-induced steatosis that were treated with H2O2. These results suggest that osthole might suppress nonalcoholic fatty liver disease by decreasing lipid accumulation, and through its anti-oxidative and anti-inflammatory effects via blocked NF-κB and MAPK signaling pathways.