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

Kim, Eun Jeong; Kim, Jeeho; Lee, Min Young; Sudhanva, Muddenahalli Srinivasa; Devakumar, Sundaravinayagam; Jeon, Young Jin

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저자정보: Kim, Eun Jeong (Department of Pharmacology, School of Medicine, Chosun University) Kim, Jeeho (Department of Pharmacology, School of Medicine, Chosun University) Lee, Min Young (Department of Pharmacology, School of Medicine, Chosun University) Sudhanva, Muddenahalli Srinivasa (Department of Pharmacology, School of Medicine, Chosun University) Devakumar, Sundaravinayagam (Department of Pharmacology, School of Medicine, Chosun University) Jeon, Young Jin (Department of Pharmacology, School of Medicine, Chosun University)

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제22권 제4호

발행연도: 2014.1

수록면: 282 - 287 (6page)

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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.

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

참고문헌 (39)

참고문헌 신청

Baker, M. S / 2001 / Expressionof a dominant negative inhibitor of NF-kappaB protectsMIN6 beta-cells from cytokine-induced apoptosis / J. Surg. Res 97:117~122

Bektur, N. E / 2013 / Protectiveeffects of silymarin against acetaminophen-induced hepatotoxicityand nephrotoxicity in mice / Toxicol. Ind. Health :1~12

Broniowska, K. A / 2014 / beta-cellresponses to nitric oxide / Vitam. Horm 95:299~322

Cetkovic-Cvrlje, M / 1994 / TNF-alpha and IFN-gammapotentiate the deleterious effects of IL-1 beta on mouse pancreaticislets mainly via generation of nitric oxide / Cytokine 6:399~406

Corbett, J. A / 1992 / Nitric oxideand cyclic GMP formation induced by interleukin 1 beta in isletsof Langerhans. Evidence for an effector role of nitric oxide in isletdysfunction / Biochem. J 287:229~235

이 논문의 저자 정보

Kim, Eun Jeong

소속기관 Department of Anesthesiology and Pain Medicine, Severance Hospital

주요연구분야 의약학 > 약학

논문수 2 이용수 2

Kim, Jeeho