Zhao Quanlai, Liu Chen, Shen Xiang, Xiao Liang, Wang Hong, Liu Ping, Wang Lingting, Xu Hongguang
Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
Mol Med Rep. 2017 Apr;15(4):2280-2288. doi: 10.3892/mmr.2017.6258. Epub 2017 Feb 28.
The aim of the present study was to investigate the role of myristicin (Myr; 1‑allyl‑5‑methoxy‑3,4‑methylenedioxybenzene), an active aromatic compound isolated from nutmeg, carrot, basil, cinnamon and parsley, in hypoxia‑induced apoptosis in rat dorsal root ganglion (DRG) neurons. It was observed that Myr significantly enhanced cell viability in hypoxia‑induced DRG neurons in a dose‑dependent manner; the optimal concentration of Myr was 50 µM. Furthermore, Myr reduced the percentage of deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling‑positive neuronal cells and influenced the expression of the pro‑apoptotic gene B‑cell lymphoma 2 (Bcl‑2) associated X protein, the apoptosis protease cleaved caspase‑3 and the anti‑apoptotic gene Bcl‑2, in the hypoxia‑induced group. In addition, Myr protected against hypoxic injury in DRG neurons by inhibiting malondialdehyde and lactate dehydrogenase, however upregulating superoxide dismutase and glutathione peroxidase. Myr reduced the expression of endoplasmic reticulum stress (ERS) markers, including CCAAT/enhancer‑binding protein‑homologous protein, glucose‑related protein 78 and cleaved caspase‑12 in the hypoxia‑induced group. To the best of our knowledge, this is the first demonstration of the activity of Myr against hypoxia‑induced apoptosis in rat DRG neurons via inhibition of the ERS pathway.
本研究的目的是探究肉豆蔻醚（Myr；1-烯丙基-5-甲氧基-3,4-亚甲二氧基苯），一种从肉豆蔻、胡萝卜、罗勒、肉桂和欧芹中分离出的活性芳香化合物，在大鼠背根神经节（DRG）神经元缺氧诱导凋亡中的作用。研究发现，Myr能以剂量依赖性方式显著提高缺氧诱导的DRG神经元的细胞活力；Myr的最佳浓度为50µM。此外，Myr降低了脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性神经元细胞的百分比，并影响了缺氧诱导组中促凋亡基因B细胞淋巴瘤2（Bcl-2）相关X蛋白、凋亡蛋白酶裂解的半胱天冬酶-3和抗凋亡基因Bcl-2的表达。此外，Myr通过抑制丙二醛和乳酸脱氢酶，同时上调超氧化物歧化酶和谷胱甘肽过氧化物酶，保护DRG神经元免受缺氧损伤。Myr降低了缺氧诱导组中内质网应激（ERS）标志物的表达，包括CCAAT/增强子结合蛋白同源蛋白、葡萄糖相关蛋白78和裂解的半胱天冬酶-12。据我们所知，这是首次证明Myr通过抑制ERS途径对大鼠DRG神经元缺氧诱导的凋亡具有活性。
