Cytoprotective effects of polyphenolics on H2O2-induced cell death in SH-SY5Y cells in relation to their antioxidant activities

The cytoprotective effects of five flavonoids (quercetin, rutin, catechin, kaempferol and morin) and four hydroxycinnamic acids (caffeic, ferulic, sinapic and chlorogenic acids) were evaluated by the degree of protection they provided against H2O2-induced damage to human neuroblastoma SH-SY5Y cells. All compounds exhibited protection against H2O2-mediated cytotoxicity in a dose dependent manner. The concentration required to give a 50% reduction in cell death (EC50 value) were derived from their dose-response relationships. The cytoprotective activities of these phenolic compounds in the order of quercetin > caffeic acid > rutin > chlorogenic acid > catechin > ferulic acid > sinapic acid > morin > kaempferol. The EC50 values of the phenolic compounds were strongly related to their chemical structures. The EC50 values were compared with the antioxidant activities as determined by five different chemically based antioxidant assays [2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP) and lipid peroxidation inhibition capacity (LPIC)]. The ability of these phenolic compounds to protect from H2O2-induced SH-SY5Y cell death correlated (r(2) = 0.85) with their determined LPIC values and weakly (r(2) = 0.44) with their ABTS activities. There was no correlation between EC50 values and ORAC, FRAP or DPPH activities. The cytoprotection assay is a more biologically relevant measurement than the chemically defined antioxidant activity assays because it uses human cells as a substrate and therefore accounts for some aspects of uptake, metabolism and location of antioxidant compounds within cells.