Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-kappaB in RAW 264.7 macrophages.
In this study, the anti-inflammatory effects of flavonoids isolated from the roots of Glycyrrhiza uralensis (Leguminosae), namely, isoliquiritin (the glycoside of isoliquirigenin) and isoliquiritigenin (the aglycone of isoliquiritin) were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Isoliquiritigenin (ILG) more potently inhibited LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production than isoliquiritin (ILT). Consistent with these findings, ILG reduced the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. In addition, the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and the mRNA expression levels of these cytokines were reduced by ILG in a dose-dependent manner. Moreover, ILG attenuated the LPS-induced DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-kappaB), and this was associated with a decrease in inhibitory kappa B-alpha (IkappaB-alpha) phosphorylation and in the subsequent blocking of p65 and p50 protein translocations to the nucleus. Furthermore, ILG suppressed the phosphorylations of IkappaB kinase (IKK), ERK1/2, and p38, whereas the phosphorylation of JNK1/2 was unaffected. These results suggest that the anti-inflammatory properties of ILG are caused by iNOS, COX-2, TNF-alpha, and IL-6 down-regulation due to NF-kappaB inhibition via the suppression of IKK, ERK1/2 and p38 phosphorylation in RAW 264.7 cells.
Kim
Ji-Yeon
JY
Department of Pharmaceutical Biochemistry, Kyung-Hee University, Dongdaemun-ku, Hoegi-Dong, Seoul 130-701, South Korea.
Park
Seung Jae
SJ
Yun
Kyung-Jin
KJ
Cho
Young-Wuk
YW
Park
Hee-Juhn
HJ
Lee
Kyung-Tae
KT
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology; D047188:Chalcones / Q000302:isolation & purification / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology; D029882:Glycyrrhiza uralensis / Q000737:chemistry; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D018517:Plant Roots; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D047188:Chalcones; D005960:Glucosides; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D000072000:NF-KappaB Inhibitor alpha; C098467:neoisoliquiritin; D009569:Nitric Oxide; D002599:Chalcone; C040920:isoliquiritigenin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone