Differential inhibitory effects of baicalein and baicalin on LPS-induced cyclooxygenase-2 expression through inhibition of C/EBPbeta DNA-binding activity.
To evaluate the possible mechanisms responsible for the anti-inflammatory effects of baicalein or baicalin, lipopolysaccharide (LPS)-induced inflammatory responses in cultured Raw 264.7 cells were studied. In the present study, baicalein and baicalin, a flavonoid present in the root of Scutellaria baicalensis Georgi, were examined for their effects on LPS-induced cyclooxygenase-2 (COX-2) gene expression in Raw 264.7 macrophages. Baicalein, but not baicalin, inhibited COX-2 gene expression in LPS-induced Raw 264.7 cells. However, both polyphenolic compounds inhibited LPS-induced inducible nitric oxide synthase (iNOS) protein expression, iNOS mRNA expression, and NO production in a dose-dependent manner. To investigate the mechanism by which baicalein inhibits COX-2 gene expression, we examined activation of mitogen-activated protein kinases (MAPKs) in Raw 264.7 cells. We did not observe any significant change in the phosphorylation of MAPKs between baicalein- and baicalin-treated cells. Baicalein and baicalin had no effect on LPS-induced nuclear factor-kappaB (NF-kappaB) and cAMP response element binding protein (CREB) DNA binding activity. Baicalein, but not baicalin, significantly inhibited the DNA binding activity of CCAAT/enhancer binding protein beta (C/EBPbeta) These results indicated that differential effects of baicalein and baicalin on COX-2 gene expression in LPS-induced Raw 264.7 cells were mediated through inhibition of C/EBPbeta DNA binding activity. Taken together, these results suggest that baicalein acts to inhibit inflammation through inhibition of COX-2 gene expression through blockade of C/EBPbeta DNA binding activity.
Woo
Kyung Jin
KJ
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Daegu 700-712, Republic of Korea.
Lim
Jun Hee
JH
Suh
Seong-Il
SI
Kwon
Young-Kyu
YK
Shin
Sang-Woo
SW
Kim
Sang-Chan
SC
Choi
Yung Hyun
YH
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D031364:Scutellaria baicalensis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D022782:CCAAT-Enhancer-Binding Protein-beta; D052246:Cyclooxygenase 2 Inhibitors; D004268:DNA-Binding Proteins; D044950:Flavanones; D005419:Flavonoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C038044:baicalin; C006680:baicalein; D004247:DNA; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020929:Mitogen-Activated Protein Kinase Kinases