Astilbin alleviates LPS-induced ARDS by suppressing MAPK signaling pathway and protecting pulmonary endothelial glycocalyx.
Acute respiratory distress syndrome (ARDS) is a devastating disorder that is characterized by increased vascular endothelial permeability and inflammation. Unfortunately, no effective treatment beyond supportive care is available for ARDS. Astilbin, a flavonoid compound isolated from Rhizoma Smilacis Glabrae, has been used for anti-hepatic, anti-arthritic, and anti-renal injury treatments. This study examined the effects of Astilbin on pulmonary inflammatory activation and endothelial cell barrier dysfunction caused by Gram-negative bacterial endotoxin lipopolysaccharide (LPS). Endothelial cells from human umbilical veins or male Kunming mice were pretreated with Astilbin 24h before LPS stimulation. Results showed that Astilbin significantly attenuated the pulmonary histopathological changes and neutrophil infiltration 6h after the LPS challenge. Astilbin suppressed the activities of myeloperoxidase and malondialdehyde, as well as the expression of tumor necrosis factor-α and interleukin-6 in vivo and in vitro. As indices of pulmonary edema, lung wet-to-dry weight ratios, were markedly decreased by Astilbin pretreatment. Western blot analysis also showed that Astilbin inhibited LPS-induced activation of mitogen-activated protein kinase (MAPK) pathways in lung tissues. Furthermore, Astilbin significantly inhibited the activity of heparanase and reduced the production of heparan sulfate in the blood serum as determined by ELISA. These findings indicated that Astilbin can alleviate LPS-induced ARDS, which potentially contributed to the suppression of MAPK pathway activation and the degradation of endothelial glycocalyx.
Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China; Department of Biotechnology, Binzhou Medical University, Yantai 264003, Shandong Province, China.
Guiqing
G
Kong
Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.
Xiao
X
Huang
Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.
Lipeng
L
Wang
Department of Respiratory Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.
Yan
Y
Li
Department of Respiratory Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.
Ting
T
Sun
Department of Respiratory Medicine, Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.
Shasha
S
Han
Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.
Weiwei
W
Zhu
Department of Intensive Care Unit, Hulunbeier People's Hospital, Hulunbeier 021000, Inner Mongolia Autonomous Region, China.
Mingming
M
Ma
Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.
Haixiao
H
Xu
Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China.
Jiankui
J
Li
Department of Biotechnology, Binzhou Medical University, Yantai 264003, Shandong Province, China. Electronic address: xiaohua124@gmail.com.
Xiaohua
X
Zhang
Department of Cell Biology, Binzhou Medical University, Yantai 264003, Shandong Province, China. Electronic address: liuxiangyong81@gmail.com.
Xiangyong
X
Liu
Department of Intensive Care Unit Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong Province, China. Electronic address: hxicuwxz@163.com.
Xiaozhi
X
Wang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D044948:Flavonols / Q000627:therapeutic use*; D019276:Glycocalyx / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D032281:Smilax / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D044948:Flavonols; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C099069:astilbin; D020928:Mitogen-Activated Protein Kinases
Acute respiratory distress syndrome; Astilbin; Endothelial glycocalyx; Heparanase; Mitogen-activated protein kinase signaling pathways