Journal
BIOMOLECULES & THERAPEUTICS
Volume 22, Issue 4, Pages 282-287Publisher
KOREAN SOC APPLIED PHARMACOLOGY
DOI: 10.4062/biomolther.2014.072
Keywords
Silymarin; Beta cells; NO; iNOS; ERK1/2
Funding
- research funds from Chosun University
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We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-alpha, IFN-gamma, and IL-1 beta)-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-kappa B, 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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