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Front. Physiol. | doi: 10.3389/fphys.2018.00102

Neferine protects endothelial glycocalyx via mitochondrial ROS in lipopolysaccharide-induced acute respiratory distress syndrome

  • 1Binzhou Medical University, China
  • 2Affiliated Hospital of Binzhou Medical University, China
  • 3Shanghai Institute of Applied Physics, China

Damage to the endothelial glycocalyx is a critical factor in increased pulmonary vascular permeability, which is the basic pathological feature of acute respiratory distress syndrome (ARDS). Neferine (Nef), a bisbenzylisoquinoline alkaloid isolated from green seed embryos of Nelumbo nucifera Gaertn, has extensive pharmacological activity. In this study, we showed that Nef reduced lung-capillary permeability, down-regulated the production of cytokines (IL-1β, IL-6, TNF-α and IL-10) and inhibited the activation of the NF-κB signaling pathway in mice with lipopolysaccharide (LPS)-induced ARDS. Further analysis indicated that Nef provided protection against endothelial glycocalyx degradation in LPS-induced ARDS mice (in vivo) and in LPS-stimulated human umbilical vein endothelial cells (in vitro). The glycocalyx-protective effect of Nef may be initiated by suppressing the production of mitochondrial ROS (mtROS) and decreasing oxidative damage. Nef was also found to promote glycocalyx restoration by accelerating the removal of mtROS in endothelial cells in LPS-induced ARDS. These results suggested the potential of Nef as a therapeutic agent for ARDS associated with Gram-negative bacterial infections and elucidated the mechanisms underlying the protection and restoration of the endothelial glycocalyx.

Keywords: Acute Respiratory Distress Syndrome, Neferine, endothelial glycocalyx, lipopolysaccharide, Mitochondrial ROS

Received: 06 Nov 2017; Accepted: 31 Jan 2018.

Edited by:

Nicola J. Brown, University of Sheffield, United Kingdom

Reviewed by:

Vincenzo Lionetti, Sant'Anna School of Advanced Studies, Italy
Suowen Xu, University of Rochester, United States  

Copyright: © 2018 Liu, Xu, Zhang, Li, Ma, Huang, Lu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Xiangyong Liu, Binzhou Medical University, Yantai, China,