Rapeseed Protein-Derived Antioxidant Peptide Rap Ameliorates Nonalcoholic Steatohepatitis and Related Metabolic Disorders in Mice

Rapeseed protein hydrolysates have recently shown in vitro antioxidant and anti-inflammatory activities. However, scant data exist about their in vivo activities. Here we report that the peptide DHNNPQIR (hereinafter referred to as RAP-8), a natural peptide derived from rapeseed protein, has excellent in vivo efficacy in mouse models of nonalcoholic steatohepatitis (NASH) and liver fibrosis. We demonstrated that RAP-8 significantly reduced hepatic steatosis and improved insulin resistance and lipid metabolism. Furthermore, RAP-8 showed markedly reduced hepatic inflammation, fibrosis, liver injury, and metabolic deterioration. In particular, RAP-8 directly suppressed expression of fibrosis-related genes α-smooth muscle actin (α-Sma) and collagen type I (Col-1α) in the liver of mice in vivo. In addtion, RAP-8 significantly decreased macrophage infiltration and reduced secretion of proinflammatory cytokines. Finally, we found that RAP-8 administration significantly decreased oxidative stress-induced apoptosis in liver injury induced by CCl4. Therefore, our results suggest that RAP-8 could be an attractive therapeutic candidate for treatment of NASH and NASH-related metabolic deterioration. Funding Statement: The Program for Guangdong Introducing Innovative and Enterpreneurial Teams (2016ZT06Y337). X.J. supported by the Thousand Young Talents Program. Declaration of Interests: All authors participated in this study declare no potential, perceived, or real conflict of interest and have agreed to the content of this manuscript. Ethics Approval Statement: The experimental procedure used in this study met the guidelines of the Animal Care and Use Committee of the Sun Yat-sen University.