Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway.
- Author:
Eun Jeong KIM
1
;
Jeeho KIM
;
Min Young LEE
;
Muddenahalli Srinivasa SUDHANVA
;
Sundaravinayagam DEVAKUMAR
;
Young Jin JEON
Author Information
1. Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea. yjjeon@chosun.ac.kr
- Publication Type:Original Article
- Keywords:
Silymarin;
Beta cells;
NO;
iNOS;
ERK1/2
- MeSH:
Blotting, Western;
Gene Expression;
Insulin-Secreting Cells*;
Milk Thistle;
NF-kappa B;
Nitric Oxide;
Phosphorylation;
Silymarin*;
Tumor Necrosis Factor-alpha
- From:Biomolecules & Therapeutics
2014;22(4):282-287
- CountryRepublic of Korea
- Language:English
-
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.