Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Neurosurgery, Taipei City Hospital Ren-Ai Branch, Taipei, Taiwan.
Department of Biochemistry, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
Evid Based Complement Alternat Med. 2013;2013:354840. doi: 10.1155/2013/354840. Epub 2013 Dec 24.
Cerebral ischemia is a leading cause of mortality and morbidity worldwide, which results in cognitive and motor dysfunction, neurodegenerative diseases, and death. Evodiamine (Evo) is extracted from Evodia rutaecarpa Bentham, a plant widely used in Chinese herbal medicine, which possesses variable biological abilities, such as anticancer, anti-inflammation, antiobesity, anti-Alzheimer's disease, antimetastatic, antianoxic, and antinociceptive functions. But the effect of Evo on ischemic stroke is unclear. Increasing data suggest that activation of autophagy, an adaptive response to environmental stresses, could protect neurons from ischemia-induced cell death. In this study, we found that Evo induced autophagy in U87-MG astrocytes. A scavenger of extracellular calcium and an antagonist of transient receptor potential vanilloid-1 (TRPV-1) decreased the percentage of autophagy accompanied by an increase in apoptosis, suggesting that Evo may induce calcium-mediated protective autophagy resulting from an influx of extracellular calcium. The same phenomena were also confirmed by a small interfering RNA technique to knock down the expression of TRPV1. Finally, Evo-induced c-Jun N-terminal kinases (JNK) activation was reduced by a TRPV1 antagonist, indicating that Evo-induced autophagy may occur through a calcium/c-Jun N-terminal kinase (JNK) pathway. Collectively, Evo induced an influx of extracellular calcium, which led to JNK-mediated protective autophagy, and this provides a new option for ischemic stroke treatment.
脑缺血是全球范围内导致死亡率和发病率的主要原因，可导致认知和运动功能障碍、神经退行性疾病和死亡。吴茱萸碱（Evo）是从吴茱萸（Evodia rutaecarpa Bentham）中提取的，这种植物广泛应用于中药，具有多种生物学功能，如抗癌、抗炎、抗肥胖、抗老年痴呆症、抗转移、抗缺氧和镇痛作用。但 Evo 对缺血性中风的影响尚不清楚。越来越多的数据表明，自噬的激活，即对环境压力的适应性反应，可保护神经元免受缺血引起的细胞死亡。在本研究中，我们发现 Evo 可诱导 U87-MG 星形胶质细胞发生自噬。细胞外钙清除剂和瞬时受体电位香草醛 1（TRPV1）拮抗剂降低了自噬的百分比，同时增加了细胞凋亡，这表明 Evo 可能通过细胞外钙内流诱导钙介导的保护性自噬。用小干扰 RNA 技术敲低 TRPV1 的表达也证实了同样的现象。最后，TRPV1 拮抗剂可降低 Evo 诱导的 c-Jun N-末端激酶（JNK）激活，表明 Evo 诱导的自噬可能通过钙/JNK 通路发生。综上所述，Evo 诱导细胞外钙内流，导致 JNK 介导的保护性自噬，这为缺血性中风的治疗提供了新的选择。
