Luo Yingdi, Lu Yanhua
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, PR China.
Pharmazie. 2012 Sep;67(9):798-803.
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.
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。