Zhong Kai-Lun, Lu Min-Yi, Liu Fei, Mei Ying, Zhang Xue-Ju, Zhang Hao, Zan Jie, Sun Xiao-Ou, Tan Wen
Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China.
Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China.
J Stroke Cerebrovasc Dis. 2019 Jan;28(1):175-184. doi: 10.1016/j.jstrokecerebrovasdis.2018.09.020. Epub 2018 Oct 24.
Stevioside, isolated from the herb Stevia rebaudiana, has been widely used as a food sweetener all over the world. Isosteviol Sodium (STV-Na), an injectable formulation of isosteviol sodium salt, has been proved to possess much greater solubility and bioavailability and exhibit protective effects against cerebral ischemia injury in vivo by inhibiting neuron apoptosis. However, the underlying mechanisms of the neuroprotective effects STV-Na are still not completely known. In the present study, we investigated the effects of STV-Na on neuronal cell death caused by hypoxia in vitro and its underlying mechanisms.
We used cobalt chloride (CoCl) to expose mouse neuroblastoma N2a cells to hypoxic conditions in vitro.
Our results showed that pretreatment with STV-Na (20 μM) significantly attenuated the decrease of cell viability, lactate dehydrogenase release and cell apoptosis under conditions of CoCl-induced hypoxia. Meanwhile, STV-Na pretreatment significantly attenuated the upregulation of intracellular Ca concentration and reactive oxygen species production, and inhibited mitochondrial depolarization in N2a cells under conditions of CoCl-induced hypoxia. Furthermore, STV-Na pretreatment significantly downregulated expressions of nitric oxide synthase, interleukin-1β, tumor necrosis factor-α, interleukin-6, nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) signalings in N2a cells under conditions of CoCl-induced hypoxia.
Taken together, STV-Na protects neural cells against hypoxia-induced apoptosis through inhibiting MAPK and NF-κB pathways.
甜菊糖苷是从甜叶菊中分离出来的，已在全球广泛用作食品甜味剂。异甜菊醇钠（STV-Na）是异甜菊醇钠盐的注射用制剂，已被证明具有更高的溶解度和生物利用度，并通过抑制神经元凋亡在体内对脑缺血损伤具有保护作用。然而，STV-Na神经保护作用的潜在机制仍不完全清楚。在本研究中，我们研究了STV-Na对体外缺氧诱导的神经元细胞死亡的影响及其潜在机制。
我们使用氯化钴（CoCl）使小鼠神经母细胞瘤N2a细胞在体外暴露于缺氧条件。
我们的结果表明，用STV-Na（20μM）预处理可显著减轻CoCl诱导的缺氧条件下细胞活力的降低、乳酸脱氢酶释放和细胞凋亡。同时，STV-Na预处理可显著减轻CoCl诱导的缺氧条件下N2a细胞内Ca浓度的上调和活性氧的产生，并抑制线粒体去极化。此外，STV-Na预处理可显著下调CoCl诱导的缺氧条件下N2a细胞中一氧化氮合酶、白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-6、核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路的表达。
综上所述，STV-Na通过抑制MAPK和NF-κB信号通路保护神经细胞免受缺氧诱导的凋亡。
