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2',4'-二羟基-6'-甲氧基-3',5'-二甲基查耳酮通过改善线粒体功能抑制MIN6细胞凋亡。

2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone inhibits apoptosis of MIN6 cells via improving mitochondrial function.

作者信息

Luo Yingdi, Lu Yanhua

机构信息

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, PR China.

出版信息

Pharmazie. 2012 Sep;67(9):798-803.

Abstract

Mitochondrial dysfunction due to oxidative stress and concomitant beta-cell apoptosis may play a key role in type 2 diabetes. Inhibiting beta-cell apoptosis through ameliorating oxidative mitochondrial dysfunction with specific natural products may have preventive or therapeutic potential. In this study, the anti-apoptotic effect of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a isolated chalcone from the buds of Cleistocalyx operculatus, on H2O2 induced MIN6 cells damage was investigated. Exposure to H2O2 at 250 microM for 3 h, the viability of MIN6 cells was significantly decreased and the apoptosis apparently occurred. A pre-treatment with DMC at the concentrations of 12.5-25 microM, before H2O2 addition, reduced nucleus fragmentation, decreased endogenous reactive oxygen species (ROS) production, and improved mitochondrial potential (MMP), and consequently, inhibited apoptosis. Furthermore, decreased activities of caspase-3 and caspase-9 were observed. These results clearly demonstrated DMC protected MIN6 cells against apoptosis due to its highly protective effect on mitochondria, and thus, it has great potential as a candidate drug for the diabetes care.

摘要

由氧化应激导致的线粒体功能障碍以及随之而来的β细胞凋亡可能在2型糖尿病中起关键作用。通过特定天然产物改善线粒体氧化功能障碍来抑制β细胞凋亡可能具有预防或治疗潜力。在本研究中,对从水翁花蕾中分离得到的查耳酮2',4'-二羟基-6'-甲氧基-3',5'-二甲基查耳酮(DMC)对H2O2诱导的MIN6细胞损伤的抗凋亡作用进行了研究。在250微摩尔/升的H2O2中暴露3小时后,MIN6细胞的活力显著降低,且明显发生凋亡。在添加H2O2之前,用浓度为12.5 - 25微摩尔/升的DMC进行预处理,可减少细胞核碎片化,降低内源性活性氧(ROS)的产生,并改善线粒体膜电位(MMP),从而抑制凋亡。此外,还观察到半胱天冬酶-3和半胱天冬酶-9的活性降低。这些结果清楚地表明,DMC对线粒体具有高度保护作用,从而保护MIN6细胞免受凋亡,因此,它作为糖尿病治疗候选药物具有巨大潜力。

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