1.Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway.
Eun Jeong KIM ; Jeeho KIM ; Min Young LEE ; Muddenahalli Srinivasa SUDHANVA ; Sundaravinayagam DEVAKUMAR ; Young Jin JEON
Biomolecules & Therapeutics 2014;22(4):282-287
We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-alpha, IFN-gamma, and IL-1beta)-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-kappaB, 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.
Blotting, Western
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Gene Expression
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Insulin-Secreting Cells*
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Milk Thistle
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NF-kappa B
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Nitric Oxide
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Phosphorylation
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Silymarin*
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Tumor Necrosis Factor-alpha