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KMID : 0606920130210040258
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Biomolecules & Therapeutics
2013 Volume.21 No. 4 p.258 ~ p.263
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Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells
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Youn Cha-Kyung
Park Seon-Joo
Lee Min-Young
Cha Man-Jin
Kim Ok-Hyeun
You Ho-Jin
Chang In-Youp
Yoon Sang-Pill
Jeon Young-Jin
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Abstract
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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.
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KEYWORD
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Silibinin, Macrophages, p38 MAPK, Nitric oxide
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