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Rapeseed Protein-Derived Antioxidant Peptide RAP Ameliorates Nonalcoholic Steatohepatitis and Related Metabolic Disorders in Mice
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2018-12-13 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b01030 Qian Zhao 1 , Hongjiao Xu 1 , Sihua Hong 1 , Nazi Song 1 , Junqiu Xie 1, 2 , Zhibin Yan 2 , Rui Wang 2 , Pengyu Yang 3 , Xianxing Jiang 1
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2018-12-13 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b01030 Qian Zhao 1 , Hongjiao Xu 1 , Sihua Hong 1 , Nazi Song 1 , Junqiu Xie 1, 2 , Zhibin Yan 2 , Rui Wang 2 , Pengyu Yang 3 , Xianxing Jiang 1
Affiliation
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 CCl4. Therefore, our results suggest that RAP-8 could be available for treatment of NASH and NASH-related metabolic disorders as a potential therapeutic candidate.
中文翻译:
油菜籽蛋白衍生的抗氧化肽RAP改善小鼠非酒精性脂肪性肝炎和相关的代谢紊乱
油菜籽蛋白水解物最近显示出体外抗氧化和抗炎活性。但是,关于其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),一种来自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出色的体内功效。我们证明,RAP-8可显着减少肝脂肪变性并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,纤维化,肝损伤和代谢恶化。特别是,RAP-8可直接抑制体内小鼠肝脏中与纤维化相关的基因表达,包括α-平滑肌肌动蛋白(α-Sma)和I型胶原(Col-1α)。另外,RAP-8显着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给药可显着降低氧化应激诱导的CCl所致肝损伤中的细胞凋亡4。因此,我们的结果表明,RAP-8可以作为潜在的治疗候选药物用于治疗NASH和与NASH相关的代谢性疾病。
更新日期:2018-12-13
中文翻译:
油菜籽蛋白衍生的抗氧化肽RAP改善小鼠非酒精性脂肪性肝炎和相关的代谢紊乱
油菜籽蛋白水解物最近显示出体外抗氧化和抗炎活性。但是,关于其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),一种来自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出色的体内功效。我们证明,RAP-8可显着减少肝脂肪变性并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,纤维化,肝损伤和代谢恶化。特别是,RAP-8可直接抑制体内小鼠肝脏中与纤维化相关的基因表达,包括α-平滑肌肌动蛋白(α-Sma)和I型胶原(Col-1α)。另外,RAP-8显着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给药可显着降低氧化应激诱导的CCl所致肝损伤中的细胞凋亡4。因此,我们的结果表明,RAP-8可以作为潜在的治疗候选药物用于治疗NASH和与NASH相关的代谢性疾病。