Abstract
Purpose: To investigate the protective effects of 4, 5-O-dicaffeoylquinic acid (DCQA) isolated from Xanthium sibiricum Patr. against mouse sepsis caused by cecal ligation/puncture (CLP) in vivo, as well as the molecular mechanisms of action involved.Methods: DCQA (7.5, 15, and 30 mg/kg/day) were administered to the mice with sepsis and the survival rate was obtained. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were examined by enzyme-linked immunosorbent assay (ELISA). Subsequently, the lipopolysaccharide (LPS) neutralizing ability of DCQA (2, 4, and 8 μg/mL) was measured using limulus amebocyte lysate (LAL) test in vitro. Furthermore, the effect of DCQA (10, 20, and 40 μg/mL) on mRNA expression of TNF-α, IL-6, and IL-8 in LPS (100 ng/mL)-treated RAW 264.7 cells was assessed using quantitative real time-polymerase chain reaction (RT-qPCR) assay.Results: DCQA significantly improved the survival rate of mice with sepsis caused by CLP (35, 50, and 65 %, respectively vs. 15 % for control, p < 0.05). LPS levels fell on co-incubation with DCQA in vitro. Moreover, ELISA and RT-qPCR results revealed that DCQA treatment lowered tendency in the mRNA expression of TNF-α, IL-6, and IL-8 (p < 0.01).Conclusion: DCQA exhibits protective effects against sepsis in mice mediated by downregulating TNF-α, IL-6, and IL-8. Further studies, in animals and humans are requied to determine the safety and efficacy of DCQA in both animal and clinical management of sepsis.
 Keywords: Xanthium sibiricum, 4,5-O-Dicaffeoylquinic acid, Sepsis, Cecal ligation and puncture, Lipopolysaccharide, TNF-α, IL-6, IL-8
Highlights
Sepsis is the common cause of death and a rapid-developing critical condition with a high mortality rate (> 20 %) in the intensive care units (ICU) of hospitals [1,2]
Effect of dicaffeoylquinic acid (DCQA) on the viability of RAW 264.7 cells treated with LPS, and Tumor necrosis factor (TNF)-α, IL-6, and IL-8 mRNA expression
The RT-qPCR results (Figure 5B-D) displayed that the TNF-α, IL-6, and IL-8 were gradually decreased after incubation with DCQA (10, 20, and 40 μg/mL)
Summary
Sepsis is the common cause of death and a rapid-developing critical condition with a high mortality rate (> 20 %) in the intensive care units (ICU) of hospitals [1,2]. Weeks) obtained from Shanghai laboratory animal center (Shanghai, China) mice, were kept in plastic pages (25 ± 2 °C; 55 ± 5 % humidity). They were adapted for 7 days with free diet and distilled water. The protective effects of DCQA against CLP surgery-induced sepsis in mice, the effect of DCQA on the viability of LPS-treated RAW 264.7 cells, as well as the underlying molecular mechanisms were examined.
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