Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells.
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-α, and IL1β. 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.
DNA Damage Response Network Center, Chosun University, Gwangju 501-759 ; Departments of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759.
Cha Kyung
CK
Youn
Seon Joo
SJ
Park
Min Young
MY
Lee
Man Jin
MJ
Cha
Ok Hyeun
OH
Kim
Ho Jin
HJ
You
In Youp
IY
Chang
Sang Pil
SP
Yoon
Young Jin
YJ
Jeon
Macrophages; Nitric oxide; Silibinin; p38 MAPK