Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells.
- Author:
Cha Kyung YOUN
1
;
Seon Joo PARK
;
Min Young LEE
;
Man Jin CHA
;
Ok Hyeun KIM
;
Ho Jin YOU
;
In Youp CHANG
;
Sang Pil YOON
;
Young Jin JEON
Author Information
1. DNA Damage Response Network Center, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea. yjjeon@chosun.ac.kr
- Publication Type:Original Article
- Keywords:
Silibinin;
Macrophages;
p38 MAPK;
Nitric oxide
- MeSH:
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
- From:Biomolecules & Therapeutics
2013;21(4):258-263
- CountryRepublic of Korea
- Language:English
-
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.
