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http://dx.doi.org/10.4062/biomolther.2013.044

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

Youn, Cha Kyung (DNA Damage Response Network Center)
Park, Seon Joo (DNA Damage Response Network Center)
Lee, Min Young (DNA Damage Response Network Center)
Cha, Man Jin (Department of Pharmacology, School of Medicine, Chosun University)
Kim, Ok Hyeun (Department of Pharmacology, School of Medicine, Chosun University)
You, Ho Jin (DNA Damage Response Network Center)
Chang, In Youp (DNA Damage Response Network Center)
Yoon, Sang Pil (Department of Anatomy, School of Medicine, Jeju National University)
Jeon, Young Jin (DNA Damage Response Network Center)
Publication Information
Biomolecules & Therapeutics / v.21, no.4, 2013 , pp. 258-263 More about this Journal
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 $IL1{\beta}$. 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.
Keywords
Silibinin; Macrophages; p38 MAPK; Nitric oxide;
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Times Cited By KSCI : 4  (Citation Analysis)
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