Quercetin 3-O-beta-(2''-galloyl)-glucopyranoside inhibits endotoxin LPS-induced IL-6 expression and NF-kappa B activation in macrophages.
We previously isolated quercetin 3-O-beta-(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)-kappaB has been evidenced to play a major mechanism in the LPS-induced IL-6 expression, an effect of QG-32 on NF-kappaB activating pathway was further analyzed. QG-32 inhibited nuclear import as well as DNA binding activity of NF-kappaB complex and subsequently suppressed NF-kappaB transcriptional activity in LPS-stimulated macrophages. However, QG-32 affected neither LPS-induced inhibitory kappaB (IkappaB) degradation nor IkappaB kinase (IKK) activation. In another experiment, QG-32 inhibited expression vector encoding NF-kappaB p65 or p50-elicited IL-6 promoter activity. Taken together, QG-32 could inhibit NF-kappaB-dependent IL-6 expression, targeting nuclear translocation of NF-kappaB complex downstream IkappaB degradation. This mechanism of action would be different from that of quercetin, an aglycone of QG-32, targeting IKK upstream IkappaB degradation. Finally, this study could provide a pharmacological potential of QG-32 in the inflammatory disorders.
Kim
Byung Hak
BH
College of Pharmacy and CBITRC, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Lee
In Jeong
IJ
Lee
Hwa-Young
HY
Han
Sang-Bae
SB
Hong
Jin Tae
JT
Ahn
Byeongwoo
B
Lee
Chong-Kil
CK
Kim
Youngsoo
Y
D000818:Animals; D002460:Cell Line; D005707:Gallic Acid; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005960:Glucosides; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019664:Polygonaceae / Q000276:immunology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D005707:Gallic Acid; D005960:Glucosides; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011794:Quercetin; D000093242:Interleukin-6 Inhibitors; C525669:quercetin 3-O-(2''-galloyl)glucopyranoside