Yan Xianlei, Huang Guangxiang, Liu Quan, Zheng Jiemin, Chen Hongmou, Huang Qidan, Chen Jiakang, Huang Heqing
a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
b Department of Neurosurgery , The First Affiliated Hospital of Guangxi Medical University , Nanning , China.
Pharm Biol. 2017 Dec;55(1):1171-1176. doi: 10.1080/13880209.2017.1288262.
Withaferin A (WFA) exhibits diverse pharmaceutical applications on human diseases, including rheumatoid arthritis, cancers and microbial infection.
We evaluated the neuroprotective role of WFA using a mouse model of spinal cord injury (SCI).
BALB/c mice were administrated 10 mg/kg of WFA. Gene expression was measured by real-time PCR, western blot and immunohistochemistry. Cell morphology and apoptosis were determined by H&E staining and TUNEL assay. Motor function was evaluated by the BBB functional scale for continuous 7 weeks.
WFA significantly improved neurobehavioural function and alleviated histological alteration of spinal cord tissues in traumatized mice. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) significantly increased in WFA-treated mice. Meanwhile, the expression of Nogo-A and RhoA remarkably decreased in the presence of WFA. Furthermore, the apoptotic cell death was attenuated in mice treated with WFA (31.48 ± 2.50% vs. 50.08 ± 2.08%) accompanied by decreased bax and increased bcl-2. In addition, WFA decreased the expression of pro-inflammatory mediators such as IL-1β (11.20 ± 1.96 ng/mL vs. 17.59 ± 1.42 ng/mL) and TNF-α (57.38 ± 3.57 pg/mL vs. 95.06 ± 9.13 pg/mL). The anti-inflammatory cytokines including TGF-β1 (14.32 ± 1.04 pg/mL vs. 9.37 ± 1.17 pg/mL) and IL-10 (116.80 ± 6.91 pg/mL vs. 72.33 ± 9.35 pg/mL) were elevated after WFA administration.
This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice.
印度楝素A（WFA）在人类疾病中具有多种药物应用，包括类风湿性关节炎、癌症和微生物感染。
我们使用脊髓损伤（SCI）小鼠模型评估了WFA的神经保护作用。
给BALB/c小鼠施用10mg/kg的WFA。通过实时PCR、蛋白质印迹和免疫组织化学测量基因表达。通过苏木精-伊红（H&E）染色和TUNEL测定法确定细胞形态和凋亡。连续7周通过BBB功能量表评估运动功能。
WFA显著改善了创伤小鼠的神经行为功能，并减轻了脊髓组织的组织学改变。在WFA处理的小鼠中，脑源性神经营养因子（BDNF）和胶质细胞系源性神经营养因子（GDNF）显著增加。同时，在WFA存在的情况下，Nogo-A和RhoA的表达显著降低。此外，WFA处理的小鼠中凋亡细胞死亡减少（31.48±2.50%对50.08±2.08%），同时bax减少，bcl-2增加。此外，WFA降低了促炎介质如IL-1β（11.20±1.96ng/mL对17.59±1.42ng/mL）和TNF-α（57.38±3.57pg/mL对95.06±9.13pg/mL）的表达。施用WFA后，包括TGF-β1（14.32±1.04pg/mL对9.37±1.17pg/mL）和IL-10（116.80±6.91pg/mL对72.33±9.35pg/mL）在内的抗炎细胞因子升高。
本研究表明，WFA通过抑制小鼠SCI后的细胞凋亡和炎症发挥神经保护作用。
