Elsevier

Journal of Surgical Research

Volume 209, March 2017, Pages 252-257
Journal of Surgical Research

Shock/Sepsis/Trauma/Critical Care
Protective effects of syringin against lipopolysaccharide-induced acute lung injury in mice

https://doi.org/10.1016/j.jss.2016.10.027Get rights and content

Abstract

Background

Syringin, a major active substance isolated from Eleutherococcus senticosus, has been found to have anti-inflammatory effect. The aim of this study was to investigate the effects and underlying mechanisms of syringin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.

Methods

We established an LPS-induced ALI model in mice. We also detected the lung wet-to-dry ratio, myeloperoxidase activity, and inflammatory cytokines tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6 to estimate the index of lung injury in mice. Furthermore, the expression of nuclear factor-erythroid 2-related factor-2 (Nrf2), heme oxygenase-1, and nuclear factor κB (NF-κB) was detected by Western blot analysis.

Results

The results showed that the increases in lung wet-to-dry ratio, myeloperoxidase activity, malondialdehyde content, and levels of tumor necrosis factor alpha, IL-1β, and IL-6 induced by LPS were significantly inhibited by treatment of syringin. The phosphorylation of IκB-α and p65 NF-κB caused by LPS was inhibited by syringin. Furthermore, syringin was found to upregulate the expression of Nrf2 and heme oxygenase 1.

Conclusions

In conclusion, the results suggest that syringin protects against LPS-induced ALI by activating Nrf2 and inhibiting NF-κB signaling pathway.

Introduction

Acute lung injury (ALI) is a critical illness syndrome with high morbidity and mortality in critically ill patients.1 ALI is characterized by severe lung inflammation and increased capillary permeability.2 Lipopolysaccharide (LPS) has been identified as the major factor that leads to ALI.3 In mice with ALI, LPS significantly upregulates the expression of inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6.4 Studies showed that these cytokines cause the aggregation of neutrophilic leukocytes and lead to lung injury.5 Therefore, inhibition of these cytokines has drawn a great attention in the treatment of LPS-induced ALI. Nuclear factor κB (NF-κB) is a nuclear transcription factor, which plays an important role in the regulation of inflammatory cytokines.6, 7 Inhibition of NF-κB activation has the ability to attenuate LPS-induced ALI.8, 9

Syringin is a major active substance isolated from Eleutherococcus senticosus. It has been found that syringin has broad pharmacologic effects, such as anti-inflammatory and antinociceptive effects.10 Syringin has been reported to protect against LPS and D-galactosamine–induced hepatic failure.11 Syringin also inhibits LPS-induced TNF-α production in RAW264.7 cells.12 Furthermore, syringin has been reported to exert sleep-potentiating effects through the nitric oxide synthases–nitric oxide pathway.13 However, the effects of syringin on LPS-induced ALI have not been reported. Therefore, in this study, we investigated the effects of syringin on LPS-induced ALI in mice.

Section snippets

Reagents

Mouse TNF-α, IL-6, and IL-1β enzyme-linked immunosorbent assay (ELISA) kits were purchased from BioLegend (San Diego, CA). The myeloperoxidase (MPO) determination kit was purchased by the Jiancheng Bioengineering Institute of Nanjing (Jiangsu, China). Mouse nuclear factor-erythroid 2-related factor-2 (Nrf2), HO-1, NF-κB p65, NF-κB p-p65, IκB, p-IκB, and β-actin were provided from Cell Signaling Technology Inc (Beverly, MA). Syringin was purchased from Chengdu Must Bio-technology Co, Ltd

Syringin reduces LPS-induced lung edema in mice

Lung W/D ratio was used to assess the effects of syringin on lung edema. As shown in Figure 1, the lung W/D ratio was dramatically higher after LPS challenged compared with the control group. However, the increase induced by LPS was dose dependently inhibited by treatment of syringin.

Syringin ameliorates LPS-induced MPO activity and MDA content

MPO activity and MDA content were used to assess the neutrophil accumulation and the oxidative stress within lung tissues. In this study, our results showed that the MPO activity and MDA content increased

Discussion

LPS-induced ALI is characterized by severe inflammatory response in lung tissues. Syringin has been reported to have anti-inflammatory effects. However, whether syringin has anti-inflammatory effects on LPS-induced ALI remains unclear. Here, we attempted to investigate the effects of syringin on LPS-induced ALI in mice.

LPS-induced ALI model in mice is characterized by the intra-alveolar and interstitial edema, alveolar hemorrhage, and overwhelming lung inflammation, which ideally imitate the

Acknowledgment

Authors' contributions: A.Z. and H.W. contributed to the conception and design. A.Z. and Z.L. did the analysis and interpretation. L.S. did the data collection. A.Z. and H.W. wrote the article and did the critical revision of the article.

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