Protective effects of neoagarotetraose against oxidative stress via Nrf2/HO-1 signaling pathway in hydrogen peroxide-induced HepG2 cells

Neoagarooligosaccharides (NAOS), possessing a variety of bioactivities, are mainly produced by β-agarases cleaving the β-1,4-glycosidic bond of agar or agarose. Previous study indicated that NAOS has antioxidant effect, however, the NAOS monomers on the activity of scavenging ROS has not been deeply clarified till now. In this study, the protective effects of NAOS especially neoagarotetraose (NA4) against H2O2-stimulated oxidative damage in HepG2 cells and their underlying molecular mechanism were investigated. The results indicated that NA4 could inhibit the production of reactive oxygen species (ROS) and enhance the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in H2O2-induced HepG2 cells. Moreover, NA4 activated the mRNA and protein expression levels of the nuclear factor erythroid-2-related factor 2 (Nrf2), which further up-regulated the mRNA and protein expression of the downstream antioxidant enzymes including heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), indicating that NA4 could attenuate H2O2-induced oxidative damage through Nrf2 pathway in HepG2 cells. The study suggested that NA4 could be an effective antioxidant candidate and it may be developed as a promising component in healthy food exerting antioxidation effect.