Chen Fangyi, Wu Rongbo, Zhu Zhu, Yin Wangping, Xiong Min, Sun Jianwei, Ni Miaozhong, Cai Guoping, Zhang Xinchao
Department of Orthopedics, Affiliated Jinshan Hospital, Fudan University, Shanghai, 201508, People's Republic of China.
J Mol Neurosci. 2015 Apr;55(4):995-1005. doi: 10.1007/s12031-014-0456-7. Epub 2014 Nov 23.
Endoplasmic reticulum (ER) stress has been demonstrated to contribute to neurodegeneration in multiple nervous system diseases. Wogonin is a flavonoid isolated from Scutellaria baicalensis root and has multiple pharmacological effects, including anti-inflammatory, antioxidant, and anticancer effects. It has a protective role in nervous system diseases; however, the pharmacological function of wogonin in the spinal cord is still with limited acquaintance. In the present study, rat dorsal root ganglion (DRG) neurons were pretreated with different concentrations of wogonin (0-100 μM) before inducing ER stress using tunicamycin (TUN) (0.75 μg/ml). Wogonin pretreatment at 75 and 100 μM had a cytoprotective effect on cells against TUN-induced toxicity. Wogonin also decreased the number of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive DRG neurons and increased expression of superoxide dismutase (SOD), which was accompanied by decreased malondialdehyde (MDA) level. The induction of apoptosis was prevented with reduction in expression level of Bax and concomitant increase in B cell lymphoma 2 (Bcl-2) level. Furthermore, wogonin downregulated expression level of ER stress genes coding for glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), active caspase 12, transcription factor 4 (ATF4), and phosphorylation of pancreatic ER stress kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α). The current study indicated that wogonin modulated stress-responsive genes, helping DRG neurons prevent TUN-induced ER stress through the PERK-eIF2α-ATF4 signaling pathway.
内质网（ER）应激已被证明在多种神经系统疾病中会导致神经退行性变。汉黄芩素是从黄芩根中分离出的一种黄酮类化合物，具有多种药理作用，包括抗炎、抗氧化和抗癌作用。它在神经系统疾病中具有保护作用；然而，汉黄芩素在脊髓中的药理功能仍了解有限。在本研究中，在用衣霉素（TUN）（0.75μg/ml）诱导内质网应激之前，用不同浓度的汉黄芩素（0 - 100μM）预处理大鼠背根神经节（DRG）神经元。75和100μM的汉黄芩素预处理对细胞具有抗TUN诱导毒性的细胞保护作用。汉黄芩素还减少了末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）阳性的DRG神经元数量，并增加了超氧化物歧化酶（SOD）的表达，同时丙二醛（MDA）水平降低。随着Bax表达水平的降低和B细胞淋巴瘤2（Bcl - 2）水平的相应增加，细胞凋亡的诱导得到了预防。此外，汉黄芩素下调了编码葡萄糖调节蛋白78（GRP78）、C/EBP同源蛋白（CHOP）、活性半胱天冬酶12、转录因子4（ATF4）的内质网应激基因的表达水平，以及胰腺内质网应激激酶（PERK）和真核起始因子2α（eIF2α）的磷酸化水平。当前研究表明，汉黄芩素调节应激反应基因，帮助DRG神经元通过PERK - eIF2α - ATF4信号通路预防TUN诱导的内质网应激。
