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KMID : 0606920140220040282
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Biomolecules & Therapeutics
2014 Volume.22 No. 4 p.282 ~ p.287
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Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway
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Kim Eun-Jeong
Kim Jee-Ho
Lee Min-Young
Sudhanva Muddenahalli Srinivasa
Devakumar Sundaravinayagam
Jeon Young-Jin
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Abstract
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We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-α, IFN-γ, and IL-1β)-induced production of nitric oxide (NO) in the pancreatic beta cell line MIN6N8a. Immunostaining and Western blot analysis showed that silymarin inhibits iNOS gene expression. RT-PCR showed that silymarin inhibits iNOS gene expression in a dose-dependent manner. We also showed that silymarin inhibits extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) phosphorylation. A MEK1 inhibitor abrogated CM-induced nitrite production, similar to silymarin. Treatment of MIN6N8a cells with silymarin also inhibited CM-stimulated activation of NF-κB, which is important for iNOS transcription. Collectively, we demonstrate that silymarin inhibits NO production in pancreatic beta cells, and silymarin may represent a useful anti-diabetic agent.
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KEYWORD
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Silymarin, Beta cells, NO, iNOS, ERK1/2
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