School of Pharmaceutical Sciences , Sun Yat-sen University , Guangzhou 510000 , China.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences , Lanzhou University , Lanzhou , China.
Mol Pharm. 2019 Jan 7;16(1):371-381. doi: 10.1021/acs.molpharmaceut.8b01030. Epub 2018 Dec 21.
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 bioactive peptide originated from rapeseed protein, exhibits excellent in vivo efficacy in mouse models of nonalcoholic steatohepatitis (NASH) and hepatic 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 fibrosis-associated gene expression, including 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 pro-inflammatory cytokines secretion. Finally, we found that RAP-8 administration significantly decreased oxidative stress-induced apoptosis in liver injury induced by CCl. Therefore, our results suggest that RAP-8 could be available for treatment of NASH and NASH-related metabolic disorders as a potential therapeutic candidate.
油菜籽蛋白水解物最近在体外显示出抗氧化和抗炎活性。然而，关于它们体内活性的数据很少。在这里，我们报告说，肽 DHNNPQIR（以下简称 RAP-8），一种来源于油菜籽蛋白的生物活性肽，在非酒精性脂肪性肝炎 (NASH) 和肝纤维化的小鼠模型中表现出优异的体内疗效。我们证明 RAP-8 可显著减轻肝脂肪变性，改善胰岛素抵抗和脂质代谢。此外，RAP-8 显示出明显减少的肝炎症、纤维化、肝损伤和代谢恶化。特别是，RAP-8 直接抑制了与纤维化相关的基因表达，包括α-平滑肌肌动蛋白 (α-Sma) 和胶原 I 型 (Col-1α) 在体内小鼠的肝脏中。此外，RAP-8 显著减少了巨噬细胞浸润并减少了促炎细胞因子的分泌。最后，我们发现 RAP-8 给药可显著减少 CCl 诱导的肝损伤中氧化应激诱导的细胞凋亡。因此，我们的结果表明，RAP-8 可用作治疗 NASH 和 NASH 相关代谢紊乱的潜在治疗候选药物。
