Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Department of Neurology, Qionghai People's Hospital, Qionghai, China.
Pharmacol Res Perspect. 2021 Apr;9(2):e00752. doi: 10.1002/prp2.752.
Although stroke is a major human neurological disease, there is a paucity of effective neuroprotectants that can improve its treatment. Casticin is a natural monomer drug with many biological effects such as anti-inflammatory and anti-tumor actions. However, it is not clear whether it has a neuroprotective effect in ischemic stroke. In this study, the neuroprotective effect of casticin in a rat middle cerebral artery occlusion (MCAO) model was investigated. Results showed that casticin reduced the volume of the cerebral infarction, mNSS scores, swimming distance, time to find the submerged platform, and serum concentrations of TNF-α, TGF-β, IL-6 in MCAO rats. Moreover, casticin also decreased the expression of TLR4, NF-κB p65, and NF-κB p50 proteins and reversed the reduced expression of IκB protein in the brain tissue of MCAO rats. The in vitro study revealed that casticin decreased apoptosis of OGD/R-PC12 cells, reduced the expression of TLR4, NF-κB p65, and NF-κB p50, while increased IκB protein expression. In conclusion, casticin improved the neurological functions of MCAO rats via inhibiting the TLR4/NF-κB pathway and might have the potential to be developed into a neuroprotective agent for stroke patients.
尽管中风是一种主要的人类神经疾病，但目前有效的神经保护剂却很少，无法改善其治疗效果。鸡骨草素是一种具有多种生物学作用的天然单体药物，如抗炎和抗肿瘤作用。然而，目前尚不清楚它是否对缺血性中风具有神经保护作用。在本研究中，研究了鸡骨草素在大鼠大脑中动脉闭塞（MCAO）模型中的神经保护作用。结果表明，鸡骨草素可减少脑梗死体积、mNSS 评分、游泳距离、找到水下平台的时间以及 MCAO 大鼠血清中 TNF-α、TGF-β和 IL-6 的浓度。此外，鸡骨草素还降低了 TLR4、NF-κB p65 和 NF-κB p50 蛋白的表达，并逆转了 MCAO 大鼠脑组织中 IκB 蛋白的减少表达。体外研究表明，鸡骨草素可减少 OGD/R-PC12 细胞的凋亡，降低 TLR4、NF-κB p65 和 NF-κB p50 的表达，同时增加 IκB 蛋白的表达。综上所述，鸡骨草素通过抑制 TLR4/NF-κB 通路改善了 MCAO 大鼠的神经功能，可能有潜力开发成为中风患者的神经保护剂。
