Quercetin 3-O-β-(2″-galloyl)-glucopyranoside inhibits endotoxin LPS-induced IL-6 expression and NF-κB activation in macrophages

We previously isolated quercetin 3-O-β-(2″-galloyl)-glucopyranoside (QG-32) from Persicaria lapathifolia (Polygonacease) as an inhibitor of superoxide production. In the present study, QG-32 was found to inhibit interleukin (IL)-6 production in endotoxin lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. The QG-32 attenuated LPS-induced synthesis of IL-6 transcript but also inhibited IL-6 promoter activity, indicating that the compound could down-regulate LPS-induced IL-6 expression at the transcription level. Since nuclear factor (NF)-κB has been evidenced to play a major mechanism in the LPS-induced IL-6 expression, an effect of QG-32 on NF-κB activating pathway was further analyzed. QG-32 inhibited nuclear import as well as DNA binding activity of NF-κB complex and subsequently suppressed NF-κB transcriptional activity in LPS-stimulated macrophages. However, QG-32 affected neither LPS-induced inhibitory κB (IκB) degradation nor IκB kinase (IKK) activation. In another experiment, QG-32 inhibited expression vector encoding NF-κB p65 or p50-elicited IL-6 promoter activity. Taken together, QG-32 could inhibit NF-κB-dependent IL-6 expression, targeting nuclear translocation of NF-κB complex downstream IκB degradation. This mechanism of action would be different from that of quercetin, an aglycone of QG-32, targeting IKK upstream IκB degradation. Finally, this study could provide a pharmacological potential of QG-32 in the inflammatory disorders.