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Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

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Abstract

Objective

To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs).

Methods

Mice were randomly divided into control, LPS, and crocin + LPS (15, 30, and 60 mg/kg) groups. HUVECs were separated into eight groups: control, crocin, matrix metalloproteinase 9 inhibitor (MMP-9 inhib), cathepsin L inhibitor (CTL inhib), LPS, MMP-9 inhib + LPS, CTL inhib + LPS, and crocin + LPS. The potential cytotoxic effect of crocin on HUVECs was mainly evaluated through methylthiazolyldiphenyl-tetrazolium bromide assay. Histological changes were assessed via hemotoxylin and eosin staining. Lung capillary permeability was detected on the basis of wet–dry ratio and through fluorescein isothiocyanate-albumin assay. Then, protein levels were detected through Western blot analysis, immunohistochemical staining, and immunofluorescence.

Results

This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. Crocin also protected against the degradation of endothelial glycocalyx heparan sulfate and syndecan-4 by inhibiting the expressions of CTL, heparanase, and MMP-9 in vivo and in vitro. Overall, this study revealed the protective effects of crocin on LPS-induced ARDS and elaborated their underlying mechanism.

Conclusion

Crocin alleviated LPS-induced ARDS by protecting against glycocalyx damage and suppressing inflammatory signaling pathways.

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Acknowledgements

This work was supported by funding from the National Natural Science Foundation of China (no.: 81670078).

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Correspondence to Xiao-zhi Wang.

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Zhang, D., Qi, B., Zhu, W.w. et al. Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways. Inflamm. Res. (2020) doi:10.1007/s00011-019-01314-z

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Keywords

  • Crocin
  • Inflammatory responses
  • Glycocalyx damage
  • LPS
  • ARDS