The protective effect of vitexinin septic encephalopathy by reducing leukocyte-endothelial adhesion and inflammatory response.

Abstract

Despite advances in therapeutic strategies and critical care management, septic encephalopathy (SE) is still a leading cause of infection-associated death in intensive care units (ICUs). Vitexin, a flavonoids compound, exerts and anti-inflammatory effect through inhibition of proinflammatory cytokines and signaling pathways. This study aimed to explore the anti-inflammatory effects of vitexin in SE and the underlying mechanisms. An SE-inducedC57BL/6 mouse model was established via cecal ligation and puncture (CLP). Western blotting was performed to evaluate the protein expression levels of Chemokine (C-X-C motif) ligand 1 (CXCL1), fractalkine (CX3CL1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, NF-κB p65, p-NF-κB p65, and tumor necrosis factor-α (TNF-α). Flow cytometry was used to detect the expressions ofCD11a/CD18, CD11b/CD18, ICAM-1, and adherent leukocyte. The expression of ICAM-1 was detected by immunohistochemistry. An enzyme-linked immunosorbent assay was performed to evaluate the expression of monocyte chemotactic protein-1 (MCP-1), Interleukin (IL)-6, IL-8, and IL-10. In this study, we found that vitexin significantly downregulated the expression of brain endothelial chemokines CXCL1 and CX3CL1 in CLP mice, exerting a potential anti-inflammatory against SE. Our data also showed that vitexin alleviated SE primarily by relying on reducing leukocyte-endothelial adhesion via the mediation of adhesion molecules. Moreover, vitexin suppressed the expression of proinflammatory cytokines, such as MCP-1, IL-6, IL-8, TNF-α, and NF-κB p65, in the CLP mice, while the expression of the anti-inflammatory cytokine IL-10 was elevated. Overall, our study demonstrated the protective effect vitexin exerts in SE by reducing leukocyte-endothelial adhesion and inflammatory response. These findings offer a molecular basis for the potential application of vitexin in the treatment of SE and other inflammatory-mediated and immunemediated disorders.