Biomol Ther.  2013 Jul;21(4):258-263.

Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells

• Youn CK
• Park SJ
• Lee MY
• Cha MJ
• Kim OH
• You HJ
• Chang IY
• Yoon SP
• Jeon YJ

Abstract

We demonstrate herein that silibinin, a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), inhibits LPS-induced activation of macrophages and production of nitric oxide (NO) in RAW 264.7 cells. Western blot analysis showed silibinin inhibits iNOS gene expression. RT-PCR showed that silibinin inhibits iNOS, TNF-alpha, and IL1beta. We also showed that silibinin strongly inhibits p38 MAPK phosphorylation, whereas the ERK1/2 and JNK pathways are not inhibited. The p38 MAPK inhibitor abrogated the LPS-induced nitrite production, whereas the MEK-1 inhibitor did not affect the nitrite production. A molecular modeling study proposed a binding pose for silibinin targeting the ATP binding site of p38 MAPK (1OUK). Collectively, this series of experiments indicates that silibinin inhibits macrophage activation by blocking p38 MAPK signaling.

Keyword

Silibinin; Macrophages; p38 MAPK; Nitric oxide

MeSH Terms

Adenosine Triphosphate
Binding Sites
Blotting, Western
Gene Expression
Macrophage Activation*
Macrophages*
MAP Kinase Signaling System
Milk Thistle
Models, Molecular
Nitric Oxide
p38 Mitogen-Activated Protein Kinases*
Phosphorylation
Tumor Necrosis Factor-alpha
Adenosine Triphosphate
Nitric Oxide
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases