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-1β. 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-1β, 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.
Highlights
Sepsis, termed as life-threatening organ dysfunction induced by polymicrobial infection, is a leading cause of death in the intensive care unit (ICU) [1, 2]
To investigate the effects of Senkyunolide I on the overall survival of mice, the cecal ligation and puncture (CLP) mice were administered with Senkyunolide I (36 mg/kg) and observed for 7 consecutive days
In the CLP+DMSO group, 13 of 24 mice survived to the seventh day (Figure 1(b)), while Senkyunolide I administration could significantly improve the survival rates of CLP mice (-20 of 24 mice survived, Figure 1(a), P = 0:0048)
Summary
Sepsis, termed as life-threatening organ dysfunction induced by polymicrobial infection, is a leading cause of death in the intensive care unit (ICU) [1, 2]. It has been reported that sleep deprivation can lead to the release of inflammatory factors, cachexia, and even death in sepsis [13,14,15]. Senkyunolide I, which is one of the effective components in an herb medicine named Ligusticum Chuanxiong hort, is mainly distributed in Sichuan province (China) and first recorded in the Divine Husbandman’s Classic of the Material Medical (Shen Nong Ben Cao Jing). The present study was performed to investigate the role of Senkyunolide I in the inflammatory level, sleep deprivation, and brain impairment in a murine model of cecal ligation and puncture (CLP)
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