Attractylone attenuates sepsis‐associated encephalopathy and cognitive dysfunction by inhibiting microglial activation and neuroinflammation. Issue 5 (22nd January 2019)

• Record Type: Journal Article
• Authors: Tian, Mi; Qingzhen, Liu; Zhiyang, Yu; Chunlong, Chen; Jiao, Duan; Zhang, Lidong; Li, Weiyan
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 5(2019)
• Page Start: 7101
• Page End: 7108
• Publication Date: 2019-01-22
• Subjects: attractylone (Atr) -- cognitive dysfunction -- microglia -- neuroinflammation -- sepsis; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27983
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Multiple studies demonstrated that sepsis is a life‐threatening state of organ dysfunction caused by infection and can induce neuroinflammation and cognitive impairment. The aim of this study was to evaluate the protective effects of attractylone (Atr) on sepsis‐associated encephalopathy (SAE) and cognitive dysfunction. Moreover, we studied the underlying molecular mechanisms. We used an LPS‐induced sepsis mouse model and evaluated the cognitive function with the Morris water maze and open field test. Neuronal damage in the hippocampus was assessed by immunohistochemical analysis. BV2 cells were used to identify the protective mechanism of Atr. The result showed that Atr attenuated LPS‐induced cognitive impairment, neural apoptosis, inflammatory factors, and microglial activation. The in vitro experiment showed that Atr promoted silent information regulator 1 (SIRT1) expression and suppressed NFκB expression. Downregulation of SIRT1 reversed the protective effect of Atr in the LPS condition. Moreover, Atr‐induced SIRT1 expression promoted BV2 from LPS‐induced M1 to M2 phenotype. Taken together, these results indicated that Atr was a potential therapeutic agent for SAE and cognitive dysfunction. Abstract : 1 Downregulation of SIRT1 reversed the protective effect of Atr in the LPS condition. 2 Atr‐induced SIRT1 expression promoted BV2 from LPS‐induced M1 to M2 phenotype.