title: Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Jeeho
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Muddenahalli Srinivasa
authors.initials: MS
authors.lastname: Sudhanva
authors.affiliation: Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Sundaravinayagam
authors.initials: S
authors.lastname: Devakumar
authors.affiliation: Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jeon
keywords: Beta cells; ERK1/2; NO; Silymarin; iNOS