Protective Effects of Rice Peptide Oryza Peptide-P60 against Oxidative Injury through Activation of Nrf2 Signaling Pathway In Vitro and In Vivo

Abstract

We previously showed that commercially available rice peptide Oryza Peptide-P60 (OP60) increased the intracellular glutathione levels. This study aimed to evaluate the antioxidant potential of this peptide and assess its mechanism of action. Pretreatment of HepG2 cells with OP60 reduced the cytotoxicity caused by H2O2 or acetaminophen (APAP) (47.7 ± 1.3% or 12.2 ± 1.3% of the cytotoxicity for 5 mg/mL OP60 pretreatment compared to that in H2O2- or APAP-treated groups, respectively; p < 0.01) through the restoration of glutathione homeostasis. Moreover, OP60 elevated the mRNA level of genes encoding heavy and light subunits of γ-glutamylcysteine synthetase (γ-GCS) by 2.9 ± 0.1-fold and 2.7 ± 0.2-fold (p < 0.001), respectively, at 8 h and also increased the level of mRNA encoding other antioxidant enzymes. Besides, OP60 promoted Nrf2 nuclear translocation by 2.2 ± 0.3-fold (p < 0.05) after 8 h. Conversely, knockdown of Nrf2 inhibited the increase of the intracellular glutathione levels and suppressed the induction of antioxidant enzyme expression by OP60. In animal studies, OP60 prevented APAP-induced liver injury by suppressing glutathione depletion (from 0.19 ± 0.02 mmol/mg protein to 0.90 ± 0.02 mmol/mg protein; p < 0.01, by pretreatment with 500 mg/kg OP60) and increasing heavy subunit of γ-GCS and heme oxygenase-1 expression in the liver. Our results indicated that OP60 exhibits a cytoprotective effect via the Nrf2 signaling pathway and is one of the few peptides with excellent antioxidant properties.

Cytoprotective Role of Edible Seahorse (Hippocampus abdominalis)-Derived Peptides in H2O2-Induced Oxidative Stress in Human Umbilical Vein Endothelial Cells

“…In this study, immunofluorescence staining results demonstrated that Nrf2 translocation and accumulation into the nucleus by pretreatment with two BAPs and their combination was augmented, thus facilitated the expression of HO-1. These results are similar to the results of recent studies [29,[36][37][38][39]. We also measured the direct antioxidant effect of two BAPs using DPPH radical scavenging assay to check that two BAPs showed the cytoprotective effect through HO-1/Nrf2 signaling.…”

MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism

“…Accumulating evidence also suggests that the Nrf2/ARE pathway reduces apoptosis and alleviates the inflammatory response, resulting in a significant improvement in tissue retention and beneficial role in coordination [ 48 ]. It is also reported that oxidative signaling and Nrf2 were tightly linked with cellular responses [ 49 ]. Previous studies have revealed mitoQ exerted its protective effects on diseases like traumatic brain injury [ 24 ], intestinal ischemia reperfusion [ 40 ] and diabetic kidney disease [ 17 ] through regulation of Nrf2.…”

Investigation of the intestinal trans-epithelial transport and antioxidant activity of two hempseed peptides WVSPLAGRT (H2) and IGFLIIWV (H3)

“…Moreover, it clearly appears that at 100 µM H2 is able to increase the Nrf-2 protein level more than basal condition (C) even in the presence of H2O2 (Figure 5A and 5C). Recently, Oryza Peptide-P60 (OP60), a commercial rice peptide, has been reported to increase intracellular glutathione levels and the evaluation of the mechanisms underlying the antioxidant potential of this peptide in HepG2 cells suggests that OP60 reduced the oxidant stress induced by H2O2 via the Nrf-2 signaling pathway (Moritani, Kawakami, Shimoda, Hatanaka, Suzaki, & Tsuboi, 2020).…”