Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, 50250 Bet Dagan, Israel.
Oxid Med Cell Longev. 2013;2013:694398. doi: 10.1155/2013/694398. Epub 2013 Aug 28.
Oxidative stress is involved in the pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Astrocytes, the most abundant glial cells in the brain, protect neurons from reactive oxygen species (ROS) and provide them with trophic support, such as glial-derived neurotrophic factor (GDNF). Thus, any damage to astrocytes will affect neuronal survival. In the present study, by activity-guided fractionation, we have purified from the desert plant Pulicaria incisa two protective compounds and determined their structures by spectroscopic methods. The compounds were found to be new chalcones-pulichalconoid B and pulichalconoid C. This is the first study to characterize the antioxidant and protective effects of these compounds in any biological system. Using primary cultures of astrocytes, we have found that pulichalconoid B attenuated the accumulation of ROS following treatment of these cells with hydrogen peroxide by 89% and prevented 89% of the H2O2-induced death of astrocytes. Pulichalconoid B exhibited an antioxidant effect both in vitro and in the cellular antioxidant assay in astrocytes and microglial cells. Pulichalconoid B also caused a fourfold increase in GDNF transcription in these cells. Thus, this chalcone deserves further studies in order to evaluate if beneficial therapeutic effect exists.
氧化应激与帕金森病和阿尔茨海默病等神经退行性疾病的发病机制有关。星形胶质细胞是大脑中最丰富的神经胶质细胞,它们可以保护神经元免受活性氧(ROS)的侵害,并为其提供营养支持,如胶质源性神经营养因子(GDNF)。因此,星形胶质细胞的任何损伤都会影响神经元的存活。在本研究中,我们通过活性导向分离,从沙漠植物 Pulicaria incisa 中纯化出两种具有保护作用的化合物,并通过光谱方法确定了它们的结构。这些化合物被发现是新的查尔酮类物质——pulichalconoid B 和 pulichalconoid C。这是首次在任何生物系统中对这些化合物的抗氧化和保护作用进行特征描述的研究。通过原代星形胶质细胞培养,我们发现 pulichalconoid B 可使细胞内 ROS 蓄积减少 89%,并可防止 89%的过氧化氢诱导的星形胶质细胞死亡。Pulichalconoid B 在体外和星形胶质细胞和小胶质细胞的细胞抗氧化测定中均表现出抗氧化作用。Pulichalconoid B 还使这些细胞中的 GDNF 转录增加了四倍。因此,这种查尔酮值得进一步研究,以评估是否存在有益的治疗效果。