Protective effects of Ulva clathrata derived polyphenols against oxidative stress in lipopolysaccharide-induced RAW 264.7 cells via Nrf2/HO-1 pathway

Ulva clathrata is a common edible seaweed along the southeast coast of China and has been widely considered beneficial for human health. In the present study we extracted polyphenols from U. clathrata, to investigate their antioxidant activity using both chemical methods and the cell-based bioassays. The results showed that polyphenol-enriched ethyl acetate fraction of U. clathrata (ECPs) and each of the six separated individual polyphenols had potent scavenging capacity for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals, as well as ferric reducing capacity, in comparison with vitamin C. The antioxidant ability of the polyphenols with the same number of benzene was positively proportional to the number of phenolic hydroxyl groups. The cell-based bioassays demonstrated that exposure to lipopolysaccharide (LPS) induced excess production of oxidative stress-related molecules, including reactive oxygen species (ROS), nitric oxide (NO) and malondialdehyde (MDA), which was significantly attenuated by the pretreatment of ECPs and three individual polyphenols, i.e., (-)-epicatechin (EC), epigallocatechin-3-O-gallate (EGCG) and (-)-epicatechin-3-O-gallate (ECG). These protective effects were shown to be achieved via activation of nuclear factor erythroid-2 related factor (Nrf2)-mediated signaling pathway, and subsequent up-regulated production and/or activity of antioxidant enzymes including heme oxygenase 1 (HO-1), catalase (CAT) and glutathione peroxidase (GSH-Px). The findings of this study suggest the potential of U. clathrata as a promising natural source of antioxidant polyphenols, and also provide a theoretical basis for their application in diverse fields related to antioxidant functions.