Four Antioxidant Peptides from Protein Hydrolysate of Red Stingray (_Dasyatis akajei_) Cartilages: Isolation, Identification, and In Vitro Activity Evaluation  
[PERSON]  
1 National Provincial Joint Laboratory of Exploration and Utilization of Marine Aquatic Genetic Resources, National Engineering Research Center of Marine Facilities Aquaculture, School of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China; [EMAIL_ADDRESS] (X.-Y.P. ); wenven  
3 kDa) from corn gluten exhibited cytoprotective effect and intracellular ROS scavenging activity in H2O2.damaged HepG2 cells because they could positively affect the activities of the intracellular antioxidant enzymes [11]. These studies suggested that APs could effectively enhance human health and/or protect food quality by reducing the oxidative stress [12]. In addition, APs can serve as ingredients of functional foods due to their nutritional and biological properties [1,13]. Collagens and peptides from porcine and cow cartilages can provide an adequate nutrient for repairing cartilage, maintain the overall health of subchondral bone and articular cartilage, and improve the joint flexibility and mobility in Osteoarthritis (OA) patients [14,15]. However, these ingredients that were used in food and medical products have caused anxiety among some consumers due to frequent outbreaks of infectious disease [15]. Therefore, cartilages from Chondrichthyes, such as sharks, skates, and rays, are thought to be one of the alternatives of porcine and cow cartilages, because they contain analogous bioactive substances, such as active proteins (angiogenesis inhibitors), proteoglycan, collagen, bioactive peptides, and elastin fibers [16, 17, 18, 19, 20, 21, 22, 23]. Furthermore, peptides from protein and collagen hydrolyses of fish cartilages showed a variety of biological activities [15,18,19]. The polypeptide (PG155) with molecular weight (MW) of 15.500 kDa from the cartilages of _Prionace glauc_ can significantly reduce the growth of subintestinal vessels (SIVs) in the zebrafish embryos model. PG155 also can inhibit vascular endothelial growth factor (VEGF) induced the migration and tubulogenesis of HUVECs [17]. FIMGPY, IVAGPQ, and IVAGPQ from _Raja porosa_ cartilages exhibited high lipid peroxidation inhibiting power and radical scavenging activities [20,21]. In addition, FIMGPY could induce the apoptosis of HeLa cells by upregulating the Bax/Bcl-2 ratio and activating caspase-3 [21]. GAERP, GEREANVM, and AEVG from protein hydrolysate of _Sphyrna lewini_ cartilages exhibited good radical scavenging activities, similar inhibiting ability on lipid peroxidation with butylated hydroxytoluene (BHT), and protection on H2O2-damaged HepG2 cells by decreasing the content of malonaldehyde (MDA) and increasing the levels of antioxidant enzymes [22]. The cartilage collagens and peptides showing significant pharmacological effects on repairing cartilage and maintaining the overall health of subchondral bones and articular cartilage collagens is more noteworthy [15,19,23]. Red stingray (_Dusyatis akajei_), which mainly resides in the northwestern Pacific Ocean, is a common species of stingray in the Dasytidae family. In previous studies, some active substances, including proteins (angiogenesis inhibitors), polysaccharides, collagens, and collagen hydrolyses, were prepared from its cartilages [16,24,25]. [PERSON] et al. reported that an angiogenesis inhibitor (DCAI-1) with a MW of 62 kDa from red stingray cartilages could inhibit the formation of the blood vessels of the chick embryo chorioallantoic membrane in a dose-dependent manner [24,26]. The mucopolysaccharides from red stingray cartilages could significantly reduce the values of total cholesterol, triglyceride, and low-density lipoprotein of blood serum, but increase the value of high-density lipoprotein cholesterol in hyperlipidaemia rabbits [27]. [PERSON] et al.