Sauchinone protects pancreatic β cells against cytokine-mediated toxicity

被引:8
作者
Jeong, Gil-Saeng [5 ]
Lee, Dong-Sung [2 ]
Park, Byung-Hyun [3 ,4 ]
Kwon, Kang-Beom [1 ]
Kim, Youn-Chul [2 ]
机构
[1] Wonkwang Univ, Dept Physiol, Sch Oriental Med, Iksan 570749, South Korea
[2] Wonkwang Univ, Coll Pharm, Iksan 570749, South Korea
[3] Chonbuk Natl Univ, Sch Med, Dept Biochem, Jeonju 561756, Jeonbuk, South Korea
[4] Chonbuk Natl Univ, Inst Med Sci, Jeonju 561756, Jeonbuk, South Korea
[5] Wonkwang Univ, Zoonosis Res Ctr, Iksan 570749, South Korea
关键词
Sauchinone; Pancreatic beta-cell; Cytokines; Cytoprotection; NF-kappa B; GSIS; NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; SAURURUS-CHINENSIS; TNF-ALPHA; C-JUN; EXPRESSION; ISLETS; TYPE-1; ACTIVATION; INTERLEUKIN-1;
D O I
10.1016/j.tiv.2010.12.004
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Sauchinone has been shown to exert potent hepatoprotective, anti-inflammatory and inhibitory effects on bone resorption. In this study, we investigated the effect of sauchinone on IL-1 beta (5 ng/ml) and IFN-gamma (100 U/mI)-induced beta-cell damage. Pre-treatment with sauchinone increased the viability of cytokine-treated RINm5F cells at concentrations of 20-40 mu M. Sauchinone prevented nitric oxide (NO) production, and this effect was correlated with reduced levels of protein expression of the inducible form of NO synthase (iNOS). The molecular mechanism by which sauchinone inhibits iNOS gene expression appeared to involve the inhibition of NF-kappa B activation. Moreover, pancreatic beta-cells treated with cytokines upregulated the phosphorylation of STAT-1, STAT-3 and STAT-5, however, pre-treatment with sauchinone attenuated these effects. Additionally, in a second set of experiments in which rat islets were used, the protective effects of sauchinone in rat islets were essentially the same as those observed when RINm5F cells were used. Sauchinone prevented cytokine-induced NO production, iNOS expression, JAK/STAT activation, and NF-kappa B activation and inhibition of glucose-stimulated insulin secretion (GSIS). Collectively, these results suggest that sauchinone can be used for the prevention of functional beta-cell damage. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:505 / 512
页数:8
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