Cytoprotective effect of lignans from Forsythia suspensa against peroxynitrite-induced LLC-PK1 cell damage

There is mounting evidence that peroxynitrite (ONOO(-)) is closely related to the pathogenesis of various diseases. As a pharmacological strategy aimed at preventing ONOO(-)-mediated toxicity, the protective activity of Forsythia suspensa (Thunb.) Vahl (Oleaceae) against ONOO(-)-induced cellular damage was investigated and its active components identified. After bioactivity-guided fractionation of its methylene chloride fraction, two tetrahydrofurofuran lignans were isolated, namely phillygenin and 8-hydroxypinoresinol. The protective effects of these lignans against ONOO(-)-induced cell death were evaluated using renal epithelial cell LLC-PK1. Phillygenin and 8-hydroxypinoresinol significantly reduced the cell injury by 3-morpholinosydnonimine (SIN-1), a ONOO(-) generator. The hydroxy substituents on the phenyl moieties may contribute to the antioxidant activities of these lignans. These results suggest that phillygenin and 8-hydroxypinoresinol may be useful for the therapeutic or preventive applications in treating ONOO(-)-related diseases.