Antioxidative effects of quercetin-glycosides isolated from the flower buds of Tussilago farfara L.

A bioassay-guided fractionation of the ethylacetate soluble fraction from the flower buds of Tussilago farfara L. (Compositae) yielded two flavonoids, quercetin 3-O-β-l-arabinopyranoside and quercetin 3-O-β-d-glucopyranoside. These two sugar conjugates of quercetin exhibited higher antioxidative activity than their aglycone, quercetin by NBT superoxide scavenging assay. Moreover, treatment with quercetin 3-O-β-l-arabinopyranoside significantly increased the total glutathione (GSH) contents and the protein level of γ-glutamylcysteine ligase (γ-GCL), a key enzyme required for glutathione (GSH) synthesis in a rat hepatocyte cell line. Subcellular fractionation and reporter gene analysis using antioxidant response element (ARE) construct revealed that quercetin 3-O-β-l-arabinopyranoside increased the level of nuclear Nrf2 and reporter activity, and that these were associated with the induction of the γ-GCL gene. After 24 h incubation of cells with quercetin 3-O-β-l-arabinopyranoside, 23% of the glycoside was converted to its aglycone, quercetin, but γ-GCL was not induced by 7 μM (23%) quercetin. These results suggest that the two quercetin-glycosides isolated from T. farfara L. have direct antioxidative properties, and that quercetin 3-O-β-l-arabinopyranoside increases the cellular GSH level by inducing the γ-GCL gene. These novel effects of quercetin-glycosides are suggestive to underlie the potential putative chemopreventive effects of T. farfara L.