Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells |
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| Authors: | Cha Kyung Youn Seon Joo Park Min Young Lee Man Jin Cha Ok Hyeun Kim Ho Jin You In Youp Chang Sang Pil Yoon Young Jin Jeon |
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| Affiliation: | 1.DNA Damage Response Network Center, Chosun University, Gwangju 501-759;2.Departments of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759;3.Departments of 3Anatomy, School of Medicine, Chosun University, Gwangju 501-759;4.4Department of Anatomy, School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea |
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| 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-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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| Keywords: | Silibinin Macrophages p38 MAPK Nitric oxide |
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