Senkyunolide I Protects against Sepsis‐Associated Encephalopathy by Attenuating Sleep Deprivation in a Murine Model of Cecal Ligation and Puncture
Jian Xie, Zhenzhen Zhao, Peng Li, Cheng‐long Zhu, Yu Guo, Jun Wang, Xiaoming Deng, Jia-feng Wang
Abstract
Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis‐associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide a sedative effect to improve sleep. However, its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP). Here, we showed that Senkyunolide I treatment improved the 7‐day survival rate and reduced the excessive release of cytokines including TNF‐ α , IL‐6, and IL‐1 β . A fear conditioning test was performed, and the results showed that Senkyunolide I attenuated CLP‐induced cognitive dysfunction. Senkyunolide I treatment also decreased the phosphorylation levels of inflammatory signaling proteins, including p‐ERK, p‐JNK, p‐P38, and p‐P65, and the level of inflammatory cytokines, including TNF‐ α , IL‐6, and IL‐1 β , in the hippocampus homogenate. Sleep deprivation was attenuated by Senkyunolide I administration, as demonstrated by the modification of the BDNF and c‐FOS expression. When sleep deprivation was induced manually, the protective effect of Senkyunolide I against inflammatory responses and cognitive dysfunction was reversed. Our data demonstrated that Senkyunolide I could protect against sepsis‐associated encephalopathy in a murine model of sepsis via relieving sleep deprivation.