AUTHOR=Xu Fenghua , Zhang Yun , Qiu Yuezi , Yang Fanghao , Liu Guoxiang , Dong Xiaolei , Chen Guang , Cao Can , Zhang Qian , Zhang Shanshan , Li Bing TITLE=Three novel antioxidant peptides isolated from C-phycocyanin against H2O2-induced oxidative stress in zebrafish via Nrf2 signaling pathway JOURNAL=Frontiers in Marine Science VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/marine-science/articles/10.3389/fmars.2022.1098091 DOI=10.3389/fmars.2022.1098091 ISSN=2296-7745 ABSTRACT=C-Phycocyanin (C-PC), a phycobiliprotein from Spirulina platensis, has been confirmed to be an effective antioxidant. However, there are few studies on their bioactive peptides. In this study, three novel active peptides, MHLWAAK(Met-His-Leu-Trp-Ala-Ala-Lys), MAQAAEYYR (Met-Ala-Gln-Ala-Ala-Glu-Tyr-Tyr-Arg), and MDYYFEER (Met-ASP-Tyr-Tyr-Phe-Glu-Glu-Arg) were isolated and purified from pancreatin hydrolysate of C-PC, its antioxidant activities and underlying molecular mechanisms were investigated. These synthesized peptides displayed high 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging ability. In addition, in a zebrafish model, the three peptides significantly protected zebrafish embryos from H2O2-induced oxidative injury without toxicity by inhibiting reactive oxygen species (ROS) generation, preventing malondialdehyde (MDA) formation, and upregulating the activities of antioxidant enzyme activities (SOD, CAT). Further experiments showed that these peptides could significantly regulated oxidative stress via activating the Keap1/Nrf2/HO-1 signaling pathway. This study indicates that the antioxidant peptides from C-PC could serve as powerful antioxidants for preventing and treating various diseases associated with oxidative stress.