Biomol Ther.  2014 Jul;22(4):282-287.

Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway

• Kim EJ
• Kim J
• Lee MY
• Sudhanva M
• Devakumar
• Jeon YJ

Abstract

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.

Keyword

Silymarin; Beta cells; NO; iNOS; ERK1/2

MeSH Terms

Blotting, Western
Gene Expression
Insulin-Secreting Cells*
Milk Thistle
NF-kappa B
Nitric Oxide
Phosphorylation
Silymarin*
Tumor Necrosis Factor-alpha
NF-kappa B
Nitric Oxide
Silymarin
Tumor Necrosis Factor-alpha