Xiaoru Yan, Jing Liu, Shu Chen, Yanan Zhu, Liang Yi, Xun Chen
By regulating the DUSP6/FOXO1 signaling, THCQ demonstrated protective effects on intestinal and BCSFB integrity, which were associated with improved cognitive outcomes in a rat model of SAE. These findings offer encouraging preclinical evidence with potential relevance.
AIMS: Sepsis-associated encephalopathy (SAE) is a clinical condition that is characterized by cognitive dysfunction induced by a systemic infection. This study was designed to assess the effect of the Taohe Chengqi decoction (THCQ) on SAE.
METHODS: THCQ (in doses ranging from low to high) was administered to rats before the CLP procedure. An evaluation of the survival, cognitive dysfunction, damage to cortical or hippocampal tissues, and intestinal permeability of septic rats was undertaken. Rat intestinal microvascular endothelial cells were exposed to lipopolysaccharide and cocultured with choroid plexus endothelial cells.
RESULTS: THCQ alleviated symptoms of SAE and reduced cerebral and hippocampal damage in rats afflicted with sepsis. THCQ reduced intestinal permeability and prevented blood-cerebrospinal fluid barrier (BCSFB) disruption through systemic circulation. THCQ inhibited DUSP6 expression, and experimental overexpression of DUSP6 exacerbated intestinal barrier disruption and increased BCSFB permeability. The interaction between DUSP6 and FOXO1 mediated the dephosphorylation of FOXO1, increasing its nuclear translocation. Inhibition of FOXO1 reversed the effect of DUSP6 overexpression on SAE.
CONCLUSION: By regulating the DUSP6/FOXO1 signaling, THCQ demonstrated protective effects on intestinal and BCSFB integrity, which were associated with improved cognitive outcomes in a rat model of SAE. These findings offer encouraging preclinical evidence with potential relevance.