Neuroprotective effect of liquiritin as an antioxidant via an increase in glucose-6-phosphate dehydrogenase expression on B65 neuroblastoma cells
Neuroprotective effect of liquiritin as an antioxidant via an increase in glucose-6-phosphate dehydrogenase expression on B65 neuroblastoma cells
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DOI：
10.1016/j.ejphar.2017.09.040
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发表时间：
2017-11-15
影响因子：
5
通讯作者：
Amano, Taku
中科院分区：
文献类型：
--
作者：
Nakatani, Yoshihiko;Kobe, Aya;Amano, Taku
甘草(甘草的根和根茎)在世界范围内被用作草药营养和草药。此外，众所周知，甘草含有多种具有生物学作用的化合物，如抗病毒、抗炎、免疫调节、抗肿瘤和神经保护作用。在甘草的各种化合物中，具有生物活性的化合物被认为包括甘草酸、甘草次酸、光滑素、甘草素和甘草素。在本研究中，我们研究了其中三种化合物(甘草酸苷、甘草苷和异甘草苷)对来源于5-羟色胺能神经元的B65神经母细胞瘤细胞的生物学作用。在这三种化合物中，只有甘草苷能促进B65神经母细胞瘤细胞的增殖。相反，甘草酸和异甘草酸都有细胞毒作用，特别是在高浓度时。用不同的细胞毒剂处理细胞，甘草素可剂量依赖性地减轻甲萘二酮硫酸钠的细胞毒作用。我们还通过评估磷酸化p44/42丝裂原活化蛋白激酶、细胞周期蛋白相关蛋白和葡萄糖-6-磷酸脱氢酶的表达水平来检测甘草酸对细胞存活的影响。甘草酸处理后，葡萄糖-6-磷酸脱氢酶蛋白表达水平呈剂量依赖性增加。相比之下，在甘草酸处理下，细胞周期蛋白相关蛋白的表达水平完全没有变化。这些结果表明，甘草中含有的甘草苷可能通过提高葡萄糖-6磷酸脱氢酶的蛋白表达水平而提高细胞的存活率。
Glycyrrhiza (the roots and rhizomes of licorice) has been used worldwide as both an herbal nutraceutical and herbal medicine. In addition, it is well known that Glycyrrhiza contains various compounds with biological effects, such as anti-viral, anti-inflammatory, immunoregulatory, anti-tumor and neuroprotective effects. Among the various compounds in Glycyrrhiza, the active compounds that show biological activity are thought to include glycyrrhizin, glycyrrhetinic acid, glabridin, licochalcones and liquiritin. In the present study, we investigated the biological effects of three of these compounds (glycyrrhizin, liquiritin and isoliquiritin) on B65 neuroblastoma cells derived from serotonergic neurons. Among these three compounds, only liquiritin enhanced the proliferation of B65 neuroblastoma cells. In contrast, both glycyrrhizin and isoliquiritin, particularly at high concentrations had cytotoxic effects. Cells were treated with various cytotoxic agents and liquiritin could ameliorate the cytotoxicity induced by menadione sodium bisulfate in a dose-dependent manner. We also examined the effect of liquiritin on cell survival by evaluating the expression levels of phospho-p44/42 mitogen-activated protein kinase, cyclin-related proteins and glucose-6-phosphate dehydrogenase, which produces nicotinamide adenine dinucleotide phosphate. Under treatment with liquiritin, the protein expression level of glucose-6-phosphate dehydrogenase increased in a dose-dependent manner. In contrast, the protein expression level of cyclin-related proteins did not change at all under treatment with liquiritin. These results suggest that liquiritin, which is contained in Glycyrrhiza, may enhance cell survival by increasing the protein expression level of glucose- 6 phosphate dehydrogenase.