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Pyropia yezoensis has been used as functional food in East Asia, especially in Korea and Japan, for more than five hundred years. This study aims to evaluate the antioxidant effect of polyphenols and proteins-rich extracts from P. yezoensis (PPPs) against 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative cell damage. Among six Korean local strains obtained from Jinhae (JiH), Haenam (HN), Jangheung (JaH), Jindo (JD), Wando (WD), and Sinan (SA) areas, the extracts of P. yezoensis from SA and JD are relatively higher in polyphenols and proteins contents. SA showed the lowest IC50 scavenging activities against 1,1-diphenyl-2-picryl-hydrazyl and alkyl radicals and displayed protective effects against reactive oxygen species (ROS) in AAPH-induced Vero cells. Especially, the PPPs extracts from SA and JD showed protective activities against AAPH-induced apoptosis, as observed by nuclear staining with Hoechst 33342. Furthermore, in vivo studies of the SA extract in zebrafish showed significantly reduced ROS generation, lipid peroxidation, and cell damage. This is the first study, to our knowledge, to evaluate the antioxidant bioactivity of PPP in the Korean Peninsula using a zebrafish model. Due to SA and JD both located in the west coast of Korea, we deduced that the chemical content of the different PPP extracts was mildly influenced by their geographic location, and this alga has potential of protective activity against AAPH-induced ROS both in vitro and in vivo. [ABSTRACT FROM AUTHOR]