Parthenolide ameliorates intracerebral hemorrhage‐induced brain injury in rats

• Published in: Phytotherapy research 2020-01, Vol.34 (1), p.153-160
• Main Authors: Wang, Jun‐an, Tong, Ming‐liang, Zhao, Bin, Zhu, Gang, Xi, Dong‐hua, Yang, Jian‐ping
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Brain; brain edema; Brain Edema - drug therapy; Brain Injuries - drug therapy; Brain injury; Caspase; Cerebral hemispheres; Cerebral Hemorrhage - complications; Cerebral Hemorrhage - drug therapy; Cytokines; Disease Models, Animal; Edema; Glutathione; Head injuries; Hemorrhage; Inflammation; Interleukins; intracranial hemorrhage (ICH); Mice; neuroinflammation; neurological deficit; Neuroprotection; Oxidative Stress; parthenolide (PN); Rats; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Superoxide dismutase; TLR4 protein; TLR4/NF‐κB signaling pathway; Toll-like receptors; Traumatic brain injury; Tumor necrosis factor
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.6510

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.