Kulasekaran Gopinath, Ganapasam Sudhandiran
Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, 600 025, India.
Mol Cell Biochem. 2015 Nov;409(1-2):199-211. doi: 10.1007/s11010-015-2525-9. Epub 2015 Aug 18.
Oxidative stress and mitochondrial dysfunction are implicated in neuronal apoptosis associated with Huntington's disease. Naringin is the flavanone present in grapefruit and related citrus species possess diverse pharmacological and therapeutic properties including antioxidant, anti-apoptotic, and neuroprotective properties. The aim of this study was to investigate the protective effect of naringin on 3-nitropropionic acid (3-NP)-induced neurotoxicity in pheochromocytoma cells (PC12) cells and to explore its mechanism of action. Naringin protects PC12 cells from 3-NP neurotoxicity, as evaluated the by cell viability assays. The lactate dehydrogenase release was decreased upon naringin treatment in 3-NP-induced PC12 cells. Naringin treatment enhances the antioxidant defense by increasing the activities of enzymatic antioxidants and the level of reduced glutathione. The increase in levels of reactive oxygen species and lipid peroxidation induced by 3-NP were significantly decreased by naringin. PC12 cells induced with 3-NP showed decrease in the mitochondrial membrane potential and mitochondrial respiratory complex enzymes, succinate dehydrogenase and cytochrome c oxidase activities, and it was significantly altered to near normal upon naringin treatment. Naringin reduced the 3-NP-induced apoptosis through the modulation in expressions of B-cell lymphoma 2 and Bcl-2-associated X protein. Further, naringin enhances the nuclear translocation of Nrf2 and induces the
NAD(P)H: quinone oxidoreductase-1 and Heme oxygenase-1 expressions through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. Taken together, the above findings suggest that naringin augments cellular antioxidant defense capacity and reduces the 3-NP-induced neurotoxicity in PC12 cells through the PI-3K/Akt-dependent Nrf2 activation in PC12 cells.
氧化应激和线粒体功能障碍与亨廷顿舞蹈病相关的神经元凋亡有关。柚皮苷是存在于葡萄柚及相关柑橘类物种中的黄烷酮，具有多种药理和治疗特性，包括抗氧化、抗凋亡和神经保护特性。本研究的目的是探讨柚皮苷对3-硝基丙酸（3-NP）诱导的嗜铬细胞瘤细胞（PC12）神经毒性的保护作用，并探索其作用机制。通过细胞活力测定评估，柚皮苷可保护PC12细胞免受3-NP神经毒性。在3-NP诱导的PC12细胞中，柚皮苷处理后乳酸脱氢酶释放减少。柚皮苷处理通过增加酶促抗氧化剂的活性和还原型谷胱甘肽水平来增强抗氧化防御。3-NP诱导的活性氧水平和脂质过氧化增加被柚皮苷显著降低。用3-NP诱导的PC12细胞显示线粒体膜电位以及线粒体呼吸复合酶、琥珀酸脱氢酶和细胞色素c氧化酶活性降低，而柚皮苷处理后这些指标显著改变至接近正常水平。柚皮苷通过调节B细胞淋巴瘤2和Bcl-2相关X蛋白的表达减少3-NP诱导的凋亡。此外，柚皮苷通过磷脂酰肌醇-3-激酶（PI3K）/Akt信号通路增强Nrf2的核转位并诱导NAD（P）H：醌氧化还原酶-1和血红素加氧酶-1的表达。综上所述，上述发现表明柚皮苷通过激活PC12细胞中PI-3K/Akt依赖的Nrf2增强细胞抗氧化防御能力并降低3-NP诱导的PC12细胞神经毒性。
