Abstract
BACKGROUND: Lycium barbarum polysaccharides (LBPs) are antioxidant and neuroprotective derivative from Wolfberry. However, whether LBP has a protective effect in non-alcoholic steatohepatitis (NASH)-induced hepatic injury is still unknown. OBJECTIVE: We aimed to study the possible hepatoprotective effects and mechanisms of LBP on a diet-induced NASH rat model. METHODS AND DESIGN: In this study, female rats were fed a high-fat diet to induce NASH with or without an oral 1 mg kg(-1) LBP feeding daily for 8 weeks. After 8 weeks, blood serum and liver samples from each rat were subjected to histological analysis, biochemical and molecular measurements. RESULTS: Compared with control rats, NASH rats showed typical NASH features including an increase in liver injury, lipid content, fibrosis, oxidative stress, inflammation and apoptosis. In contrast, NASH+LBP-co-treated rats showed (1) improved histology and free fatty acid levels; (2) re-balance of lipid metabolism; (3) reduction in profibrogenic factors through the TGF-β/SMAD pathway; (4) improved oxidative stress through cytochrome P450 2E1-dependent pathway; (5) reduction in hepatic pro-inflammatory mediators and chemokines production; and (6) amelioration of hepatic apoptosis through the p53-dependent intrinsic and extrinsic pathways. The preventive effects of LBP were partly modulated through the PI3K/Akt/FoxO1, LKB1/AMPK, JNK/c-Jun and MEK/ERK pathways and the downregulation of transcription factors in the liver, such as nuclear factor-κB and activator protein-1. CONCLUSION: LBP is a novel hepatoprotective agent against NASH caused by abnormal liver metabolic functions.