Korean J Physiol Pharmacol.  2010 Dec;14(6):353-358. 10.4196/kjpp.2010.14.6.353.

Magnolol Inhibits LPS-induced NF-kappaB/Rel Activation by Blocking p38 Kinase in Murine Macrophages

Affiliations
  • 1Department of Pharmacology, School of Medicine, Chosun University, Kwangju 501-709, Korea. yjjeon@chosun.ac.kr
  • 2Department of Bio-New Drug Development, School of Medicine, Chosun University, Kwangju 501-709, Korea.
  • 3Department of Cellular Molecular Medicine, School of Medicine, Chosun University, Kwangju 501-709, Korea.
  • 4Department of Biochemistry, School of Medicine, Inje University, Busan 614-735, Korea.

Abstract

This study demonstrates the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to inhibit LPS-induced expression of iNOS gene and activation of NF-kappaB/Rel in RAW 264.7 cells. Immunohisto-chemical staining of iNOS and Western blot analysis showed magnolol to inhibit iNOS gene expression. Reporter gene assay and electrophoretic mobility shift assay showed that magnolol inhibited NF-kappaB/Rel transcriptional activation and DNA binding, respectively. Since p38 is important in the regulation of iNOS gene expression, we investigated the possibility that magnolol to target p38 for its anti-inflammatory effects. A molecular modeling study proposed a binding position for magnolol that targets the ATP binding site of p38 kinase (3GC7). Direct interaction of magnolol and p38 was further confirmed by pull down assay using magnolol conjugated to Sepharose 4B beads. The specific p38 inhibitor SB203580 abrogated the LPS-induced NF-kappaB/Rel activation, whereas the selective MEK-1 inhibitor PD98059 did not affect the NF-kappaB/Rel. Collectively, the results of the series of experiments indicate that magnolol inhibits iNOS gene expression by blocking NF-kappaB/Rel and p38 kinase signaling.

Keyword

Magnolol; Macrophages; p38 kinase; iNOS; NF-kappaB/Rel

MeSH Terms

Adenosine Triphosphate
Binding Sites
Biphenyl Compounds
Blotting, Western
DNA
Electrophoretic Mobility Shift Assay
Flavonoids
Gene Expression
Genes, Reporter
Imidazoles
Lignans
Macrophages
Magnolia
Models, Molecular
Phosphotransferases
Pyridines
Sepharose
Transcriptional Activation
Adenosine Triphosphate
Biphenyl Compounds
DNA
Flavonoids
Imidazoles
Lignans
Phosphotransferases
Pyridines
Sepharose
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