Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, Xi'an 710069, China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an 710021, China.
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, Xi'an 710069, China.
Toxicology. 2023 Aug 15;495:153598. doi: 10.1016/j.tox.2023.153598. Epub 2023 Aug 5.
Ischemic stroke is regarded one of the most common causes of brain vulnerability. Silibinin (SIL), extracted from the seeds of Silybinisus laborinum L., has been found to exhibit obvious therapeutic effects on neurodegenerative diseases. GAS6 has been proven to have significant neuroprotective effects; however, the role of SIL and GAS6 in ischemic stroke remains unclear. This study aimed to investigate the protective effects of SIL against cerebral ischemia-reperfusion injury in neuroblastoma N2a cells, as well as the mechanisms involved. Firstly, the toxicity of SIL was evaluated, and safe concentrations were chosen for subsequent experiments. Then, SIL exerts significant neuroprotection against hypoxia/reoxygenation (HR) injury in N2a cells, as manifested by increased cell viability, decreased apoptotic rate, LDH, and ROS generation. Additionally, SIL was found to inhibit HR-induced apoptosis, mitochondria dysfunction, and oxidative stress. However, silencing of GAS6 inhibited the neuroprotective effects of SIL. To sum up, these results suggest that SIL may be a promising therapeutic agent for the treatment of ischemic stroke.
缺血性脑卒中被认为是大脑易损性的最常见原因之一。水飞蓟宾（SIL）从水飞蓟宾的种子中提取，已被发现对神经退行性疾病具有明显的治疗作用。Gas6 已被证明具有显著的神经保护作用；然而，SIL 和 Gas6 在缺血性脑卒中中的作用尚不清楚。本研究旨在探讨 SIL 对神经母细胞瘤 N2a 细胞脑缺血再灌注损伤的保护作用及其机制。首先，评估了 SIL 的毒性，并选择了安全浓度用于后续实验。然后，SIL 对 N2a 细胞缺氧/复氧（HR）损伤具有显著的神经保护作用，表现为细胞活力增加、凋亡率降低、LDH 和 ROS 生成减少。此外，SIL 还能抑制 HR 诱导的细胞凋亡、线粒体功能障碍和氧化应激。然而，Gas6 的沉默抑制了 SIL 的神经保护作用。综上所述，这些结果表明 SIL 可能是治疗缺血性脑卒中的一种有前途的治疗药物。
