Abstract
Background: Emodin is the main active component of rhubarb, which has demonstrated many beneficial effects against inflammation. Nanosilver is an effective antimicrobial agent. The present study was designed to observe the effects of Emodin combined with silver nanoparticles (E/S) on sepsis protection and related mechanism.Methods: E/S was prepared by loading different concentrations of Emodin on nanosilver and cytotoxicity of E/S were determined by suphorhodamine B assays. Anti-microbial activities of E/S were assayed by direct interaction with various common pathogens and anti-adhesive activites of E/S on leukocytes with endothelial cells were assayed by biochemical analysis. Next, inflammatory cell enumeration, inflammatory mediators in bronchoalveolar lavage fluid (BALF) and endothelial cell function were analyzed on a clinically relevant model of sepsis induced by cecal ligation and puncture (CLP) after E/S administration. The effects of E/S on NF-κB and p38 were also examined by western blot.Results: E/S exhibited little cytotoxicity action on endothelial cells and significant inhibitory activities against all tested common microorganisms and adherence between leukocyte and endothelial cells. E/S induced anti-sepsis protection mainly mediated by inhibition of inflammatory cells infiltration, down-regulation of TNF-alpha, IL-8 and lactic dehydrogenase (LDH), and inhibition of NF-κB and p38 pathways in mice 24 h post-CLP.Conclusion: Our data suggest that E/S has strong anti-sepsis effects, which was related with anti-inflammatory protection and thereby promote survival following sepsis challenge.
Highlights
Severe sepsis and septic shock are common fatal diseases with an extremely high morbidity rate for overwhelming lung inflammation in intensive care unit (Mikkelsen et al, 2013) and management of patients relies mainly on early, right and rapid therapeutic measures including administration of appropriate antibiotics, control of infection source, and resuscitation with intravenous fluids and vasoactive drugs when needed (Cohen et al, 2015)
Emodin combined with silver nanoparticles (E/S) exhibited an obvious cytotoxicity at 50 μg Emodin/1 μg nanosilver per mL, while nanosilver exhibited a dose-independent cytotoxicity with an obvious cytotoxicity at 10 μg/mL (Figure 1A)
We choose a final concentration of 20 μg/mL Emodin and1 μg/mL nanosilver to construct the combined administration
Summary
Severe sepsis and septic shock are common fatal diseases with an extremely high morbidity rate for overwhelming lung inflammation in intensive care unit (Mikkelsen et al, 2013) and management of patients relies mainly on early, right and rapid therapeutic measures including administration of appropriate antibiotics, control of infection source, and resuscitation with intravenous fluids and vasoactive drugs when needed (Cohen et al, 2015). Emodin Combined with Nanosilver Inhibited Sepsis protein kinase (MAPK) pathways, gets involved in the pathogenesis of sepsis (Carneiro et al, 2013; Liang et al, 2014). A large number of pathogens enter the blood stream, release a large number of pathogenic substances and activate serious systemic inflammatory response. Sepsis results from the combined effect of a virulent infection and powerful host response to the infection. Great efforts has been made in the inhibition of exaggerated inflammation and promotion of endothelial protection, the treatments have still been very limited and cause high mortality rates worldwide. The present study was designed to observe the effects of Emodin combined with silver nanoparticles (E/S) on sepsis protection and related mechanism
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