Pharmacological Research Center of Medicinal Plants, Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 917794-8564, Iran ; School of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
Evid Based Complement Alternat Med. 2013;2013:716730. doi: 10.1155/2013/716730. Epub 2013 Jul 7.
The discovery and development of natural products with potent antioxidant, anti-inflammatory, and antiapoptotic properties have been one of the most interesting and promising approaches in the search for the treatment of many neurodegenerative diseases including ischemic stroke. Serum/glucose deprivation (SGD) has served as an excellent in vitro model for the understanding of the molecular mechanisms of neuronal damage during ischemia and for the development of neuroprotective drugs against ischemia-induced brain injury. Recent studies suggested that pomegranate (Punica granatum L.) or its active constituents exert pharmacological actions such as antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, in this study we investigated the possible protective effects of different extracts of pomegranate against SGD-induced PC12 cells injury. Initially, the cells were pretreated with different concentrations of pulp hydroalcoholic extract (PHE), pulp aqueous extract (PAE) and pomegranate juice (PJ) for 2 h and then deprived of serum/glucose (SGD) for 6 and 12 h. SGD caused a significant reduction in cell viability (measured by the MTT assay) after 6 and 12 h, as compared with control cells (P < 0.001). Pretreatment with PHE, PAE, and PJ significantly and concentration-dependently increased cell viability following SGD insult for 6 and 12 h. A significant increase in DNA damage (measured by the comet assay) was seen in nuclei of cells following SGD for 12 h (P < 0.001). In control groups, no significant difference was seen in DNA damage between PHE, PAE, and PJ-pretreated and vehicle-pretreated PC12 cells (P > 0.05). PHE, PAE, and PJ pretreatment resulted in a significant decrease in DNA damage following ischemic insult (P < 0.001). This suppression of DNA damage by PHE, PAE and PJ was found to be concentration dependent. These data indicate that there is a cytoprotective property in PHE, PAE, and PJ under SGD condition in PC12 cells, suggesting that pomegranate has the potential to be used as a new therapeutic strategy for neurodegenerative disorders.
天然产物具有强大的抗氧化、抗炎和抗细胞凋亡特性，因此将其开发为治疗多种神经退行性疾病（包括缺血性中风）的方法一直是最有趣和最有前途的方法之一。血清/葡萄糖剥夺（SGD）已被用作理解缺血期间神经元损伤的分子机制以及开发针对缺血性脑损伤的神经保护药物的出色体外模型。最近的研究表明，石榴（Punica granatum L.）或其有效成分具有药理作用，如抗氧化、抗炎和神经保护作用。因此，在这项研究中，我们研究了石榴的不同提取物对 SGD 诱导的 PC12 细胞损伤的可能保护作用。首先，将细胞用不同浓度的果肉水醇提取物（PHE）、果肉水提取物（PAE）和石榴汁（PJ）预处理 2 小时，然后进行血清/葡萄糖剥夺（SGD）6 和 12 小时。与对照细胞相比（P < 0.001），SGD 后 6 和 12 小时，细胞活力（通过 MTT 测定）显著降低。PHE、PAE 和 PJ 预处理可显著增加 SGD 损伤后 6 和 12 小时的细胞活力，呈浓度依赖性。SGD 12 小时后，细胞核中的 DNA 损伤（通过彗星试验测量）显着增加（P < 0.001）。在对照组中，PHE、PAE 和 PJ 预处理与载体预处理的 PC12 细胞之间的 DNA 损伤无显着差异（P > 0.05）。PHE、PAE 和 PJ 预处理可显着降低缺血性损伤后的 DNA 损伤（P < 0.001）。发现 PHE、PAE 和 PJ 对 DNA 损伤的抑制作用呈浓度依赖性。这些数据表明，在 SGD 条件下，PHE、PAE 和 PJ 对 PC12 细胞具有细胞保护特性，这表明石榴具有作为神经退行性疾病新治疗策略的潜力。
