期刊
PHYTOTHERAPY RESEARCH
卷 34, 期 1, 页码 153-160出版社
WILEY
DOI: 10.1002/ptr.6510
关键词
intracranial hemorrhage (ICH); parthenolide (PN); oxidative stress; neuroinflammation; neurological deficit; brain edema; TLR4; NF-kappa B signaling pathway
资金
- Key Discipline Group Construction Project of Shanghai Pudong [PWZxq2017-02]
- Featured Clinical Discipline Project of Shanghai Pudong [PWYst2018-01]
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-alpha, 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-kappa B pathway was suppressed by PN treatment. These findings suggested that PN could be beneficial in the therapeutic strategy for ICH treatment.
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