Department of Anesthesiology, Pudong New Area People's Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, China.
Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Phytother Res. 2020 Jan;34(1):153-160. doi: 10.1002/ptr.6510. Epub 2019 Sep 9.
Neuroinflammation and oxidative stress are key contributors to intracranial hemorrhage (ICH)-induced brain injury. Parthenolide (PN) is a sesquiterpene lactone that has been observed to have antioxidative, anti-inflammatory, and neuroprotective potentials. However, the role of PN in ICH remains unclear. Therefore, we investigated the neuroprotective effects and underlying mechanisms of PN on an experimental model of ICH in rats. Our results showed that PN treatment improved neurological deficit and brain edema in ICH rats. The ipsilateral hemispheres of the brain were separated and homogenized. The concentrations of TNF-α, interleukin (IL)-6, and IL-17 in the homogenates were detected by enzyme-linked immunosorbent assay. We found that PN inhibited the production of proinflammatory cytokines in an ICH rat model. The ROS and glutathione (GSH) levels, as well as the activity of superoxide dismutase (SOD) in the homogenates were measured. ICH caused an increase in ROS level, and the decreases in GSH level and SOD activity were mitigated by PN treatment. Furthermore, PN significantly suppressed the expressions of active caspase-3 and Bax in ipsilateral hemispheres of the brain at Day 3 after ICH, as well as increased the surviving neurons. Finally, the ICH-induced activation of TLR4/NF-κB pathway was suppressed by PN treatment. These findings suggested that PN could be beneficial in the therapeutic strategy for ICH treatment.
神经炎症和氧化应激是导致脑出血(ICH)脑损伤的关键因素。小白菊内酯(PN)是一种倍半萜内酯,已被观察到具有抗氧化、抗炎和神经保护作用。然而,PN 在 ICH 中的作用尚不清楚。因此,我们研究了 PN 对大鼠 ICH 实验模型的神经保护作用及其潜在机制。结果表明,PN 治疗可改善 ICH 大鼠的神经功能缺损和脑水肿。分离并匀浆大脑的对侧半球。通过酶联免疫吸附试验检测匀浆中 TNF-α、白细胞介素(IL)-6 和 IL-17 的浓度。我们发现 PN 抑制了 ICH 大鼠模型中促炎细胞因子的产生。测量匀浆中 ROS 和谷胱甘肽(GSH)水平以及超氧化物歧化酶(SOD)的活性。ICH 导致 ROS 水平升高,PN 治疗减轻了 GSH 水平和 SOD 活性的降低。此外,PN 还显著抑制了 ICH 后第 3 天大脑对侧半球中活性 caspase-3 和 Bax 的表达,并增加了存活的神经元。最后,PN 治疗抑制了 ICH 诱导的 TLR4/NF-κB 通路的激活。这些发现表明,PN 可能有益于 ICH 治疗的治疗策略。