Biomolecules & Therapeutics  2013;21(4):258-263

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

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

Affiliations

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Keywords

Silibinin; Macrophages; p38 MAPK; Nitric oxide

Country

Republic 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.