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Glycyrrhizin protects against porcine endotoxemia through modulation of systemic inflammatory response.

Wang W, Zhao F, Fang Y, Li X, Shen L, Cao T, Zhu H - Crit Care (2013)

Bottom Line: However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response.By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Glycyrrhizin (GL) was recently found to suppress high-mobility group box 1 (HMGB1)-induced injury by binding directly to it. However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.

Methods: Twenty-one pigs were divided into four groups: sham group (n=3), control group (n=6), ethyl pyruvate group (n=6) and glycyrrhizin group (n=6). Pigs were anesthetized, mechanically ventilated, monitored and given a continuous intravenous infusion of lipopolysaccharide (LPS). Twelve hours after the start of the LPS infusion, ethyl pyruvate (30 mg/kg/hr) or glycyrrhizin (1 mg/kg/hr) was administered for 12 hours. Systemic and pulmonary hemodynamics, oxygen exchange, and metabolic status were measured. The concentrations of cytokines in serum and the corresponding gene and protein expressions in tissue samples from liver, lungs, kidneys, small intestine and lymph nodes were measured.

Results: GL maintained the stability of systemic hemodynamics and improved pulmonary oxygen exchange and metabolic status. GL also attenuated organ injury and decreased the serum levels of HMGB1 and other pro-inflammatory cytokines by inhibiting their gene and protein expression.

Conclusions: GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response. By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

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mRNA expression of ICAM-1, VCAM-1 and PBEF and protein expression of ICAM-1 and VCAM-1 in lung. A) Real-time PCR showed that the expression levels of ICAM-1, VCAM-1 and PBEF mRNA decreased significantly in the EP and GL groups compared to the control group. B) Western-blot showed that the expression levels of ICAM-1 and VCAM-1 protein decreased significantly in the EP and GL groups compared to the control group. C) Quantitative assessment of protein relative to β-actin showed that the expression levels of ICAM-1 and VCAM-1 protein decreased significantly in the EP and GL groups compared to the control group. * P < 0.05 versus the control group. EP, ethyl pyruvate; GL, glycyrrhizin; ICAM-1, intercellular adhesion molecule-1; PBEF, pre-B-cell colony-enhancing factor; VCAM-1, vascular cell adhesion molecule 1.
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Figure 3: mRNA expression of ICAM-1, VCAM-1 and PBEF and protein expression of ICAM-1 and VCAM-1 in lung. A) Real-time PCR showed that the expression levels of ICAM-1, VCAM-1 and PBEF mRNA decreased significantly in the EP and GL groups compared to the control group. B) Western-blot showed that the expression levels of ICAM-1 and VCAM-1 protein decreased significantly in the EP and GL groups compared to the control group. C) Quantitative assessment of protein relative to β-actin showed that the expression levels of ICAM-1 and VCAM-1 protein decreased significantly in the EP and GL groups compared to the control group. * P < 0.05 versus the control group. EP, ethyl pyruvate; GL, glycyrrhizin; ICAM-1, intercellular adhesion molecule-1; PBEF, pre-B-cell colony-enhancing factor; VCAM-1, vascular cell adhesion molecule 1.

Mentions: The RNA transcripts of ICAM-1, VCAM-1 and PBEF (pre-B-cell colony-enhancing factor) in the lung were significantly up-regulated by LPS compared to the sham group, whereas treatment with GL or EP reduced the extent of such up-regulation (Figure 3A). The protein of ICAM-1 and VCAM-1 in the lung showed changes similar to mRNA in the four groups (Figure 3B, C). As indicators of small intestine injury, DAO and D-lactate in serum increased due to LPS, and GL attenuated such responses with DAO and D-lactate while EP affected D-lactate only (Figure 4).


Glycyrrhizin protects against porcine endotoxemia through modulation of systemic inflammatory response.

Wang W, Zhao F, Fang Y, Li X, Shen L, Cao T, Zhu H - Crit Care (2013)

mRNA expression of ICAM-1, VCAM-1 and PBEF and protein expression of ICAM-1 and VCAM-1 in lung. A) Real-time PCR showed that the expression levels of ICAM-1, VCAM-1 and PBEF mRNA decreased significantly in the EP and GL groups compared to the control group. B) Western-blot showed that the expression levels of ICAM-1 and VCAM-1 protein decreased significantly in the EP and GL groups compared to the control group. C) Quantitative assessment of protein relative to β-actin showed that the expression levels of ICAM-1 and VCAM-1 protein decreased significantly in the EP and GL groups compared to the control group. * P < 0.05 versus the control group. EP, ethyl pyruvate; GL, glycyrrhizin; ICAM-1, intercellular adhesion molecule-1; PBEF, pre-B-cell colony-enhancing factor; VCAM-1, vascular cell adhesion molecule 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672474&req=5

Figure 3: mRNA expression of ICAM-1, VCAM-1 and PBEF and protein expression of ICAM-1 and VCAM-1 in lung. A) Real-time PCR showed that the expression levels of ICAM-1, VCAM-1 and PBEF mRNA decreased significantly in the EP and GL groups compared to the control group. B) Western-blot showed that the expression levels of ICAM-1 and VCAM-1 protein decreased significantly in the EP and GL groups compared to the control group. C) Quantitative assessment of protein relative to β-actin showed that the expression levels of ICAM-1 and VCAM-1 protein decreased significantly in the EP and GL groups compared to the control group. * P < 0.05 versus the control group. EP, ethyl pyruvate; GL, glycyrrhizin; ICAM-1, intercellular adhesion molecule-1; PBEF, pre-B-cell colony-enhancing factor; VCAM-1, vascular cell adhesion molecule 1.
Mentions: The RNA transcripts of ICAM-1, VCAM-1 and PBEF (pre-B-cell colony-enhancing factor) in the lung were significantly up-regulated by LPS compared to the sham group, whereas treatment with GL or EP reduced the extent of such up-regulation (Figure 3A). The protein of ICAM-1 and VCAM-1 in the lung showed changes similar to mRNA in the four groups (Figure 3B, C). As indicators of small intestine injury, DAO and D-lactate in serum increased due to LPS, and GL attenuated such responses with DAO and D-lactate while EP affected D-lactate only (Figure 4).

Bottom Line: However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response.By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Glycyrrhizin (GL) was recently found to suppress high-mobility group box 1 (HMGB1)-induced injury by binding directly to it. However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.

Methods: Twenty-one pigs were divided into four groups: sham group (n=3), control group (n=6), ethyl pyruvate group (n=6) and glycyrrhizin group (n=6). Pigs were anesthetized, mechanically ventilated, monitored and given a continuous intravenous infusion of lipopolysaccharide (LPS). Twelve hours after the start of the LPS infusion, ethyl pyruvate (30 mg/kg/hr) or glycyrrhizin (1 mg/kg/hr) was administered for 12 hours. Systemic and pulmonary hemodynamics, oxygen exchange, and metabolic status were measured. The concentrations of cytokines in serum and the corresponding gene and protein expressions in tissue samples from liver, lungs, kidneys, small intestine and lymph nodes were measured.

Results: GL maintained the stability of systemic hemodynamics and improved pulmonary oxygen exchange and metabolic status. GL also attenuated organ injury and decreased the serum levels of HMGB1 and other pro-inflammatory cytokines by inhibiting their gene and protein expression.

Conclusions: GL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response. By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

Show MeSH
Related in: MedlinePlus