PMID- 30171880 OWN - NLM STAT- MEDLINE DCOM- 20181015 LR - 20211204 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 210 DP - 2018 Oct 1 TI - Honokiol protects pulmonary microvascular endothelial barrier against lipopolysaccharide-induced ARDS partially via the Sirt3/AMPK signaling axis. PG - 86-95 LID - S0024-3205(18)30526-5 [pii] LID - 10.1016/j.lfs.2018.08.064 [doi] AB - AIMS: Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia with diffuse alveolar damage and increased pulmonary microvascular permeability. Honokiol (HKL), the principal active ingredient of Chinese herb magnolia officinalis, protected the lung of experimental ARDS models via attenuation of inflammation and oxidative stress. However, whether HKL has protective effects against the dysfunction of pulmonary microvascular endothelial barrier and the potential mechanisms remain unclear. MAIN METHODS: In the present study, we examined the levels of plasma Angiopoietin-2 (Ang-2) in ARDS patients, explored the effects of HKL on the vascular endothelial barrier at the ARDS animal and cell levels. KEY FINDINGS: Our data showed that compared with the healthy controls, circulating Ang-2 level was higher in the patients with ARDS, and were usually supposed to be positively related to the severity of ARDS. Moreover, HKL effectively inhibited lung inflammatory injury and microvascular leakage, and improved ARDS mice survival. HKL also inhibited the expression of Ang-2, ICAM-1 and VCAM-1, and restored the expression of Sirt3, beta-Catenin and VE-Cadherin. Furthermore, HKL improved ECs survival and inhibited the apoptosis of ECs. The inhibition of Ang-2 expression in vitro by HKL is accompanied by the upregulation of Sirt3 and AMPK phosphorylation. SIGNIFICANCE: Our data demonstrated that HKL protected pulmonary microvascular endothelial barrier against LPS-induced ARDS at least in part through activating the Sirt3/AMPK signaling and inhibiting the Ang-2 expression. Thus, our findings show that the activation of Sirt3 signaling is a potential mechanism for the protective effects of HKL on vascular barrier. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Chen, Lan AU - Chen L AD - Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. FAU - Li, Wen AU - Li W AD - Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. FAU - Qi, Di AU - Qi D AD - Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. FAU - Lu, Ling AU - Lu L AD - Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. FAU - Zhang, Zhengwei AU - Zhang Z AD - Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. FAU - Wang, Daoxin AU - Wang D AD - Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: wangdaoxin01@126.com. LA - eng PT - Journal Article DEP - 20180829 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (ANGPT2 protein, human) RN - 0 (Angiopoietin-2) RN - 0 (Biphenyl Compounds) RN - 0 (Enzyme Inhibitors) RN - 0 (Lignans) RN - 0 (Lipopolysaccharides) RN - 0 (Sirt3 protein, mouse) RN - 11513CCO0N (honokiol) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases) RN - EC 3.5.1.- (Sirtuin 3) SB - IM MH - AMP-Activated Protein Kinase Kinases MH - Angiopoietin-2/metabolism MH - Animals MH - Apoptosis/drug effects MH - Biphenyl Compounds/*pharmacology MH - Capillary Permeability/*drug effects MH - Case-Control Studies MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Endothelium, Vascular/*drug effects/metabolism/pathology MH - Enzyme Inhibitors/pharmacology MH - Humans MH - Lignans/*pharmacology MH - Lipopolysaccharides/*toxicity MH - Lung/*blood supply MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Protein Kinases/*metabolism MH - Respiratory Distress Syndrome/chemically induced/metabolism/pathology/*prevention & control MH - Signal Transduction MH - Sirtuin 3/*metabolism OTO - NOTNLM OT - ARDS OT - Ang-2 OT - Honokiol OT - Pulmonary microvascular endothelial barrier OT - Sirt3 EDAT- 2018/09/02 06:00 MHDA- 2018/10/16 06:00 CRDT- 2018/09/02 06:00 PHST- 2018/07/11 00:00 [received] PHST- 2018/08/27 00:00 [accepted] PHST- 2018/09/02 06:00 [pubmed] PHST- 2018/10/16 06:00 [medline] PHST- 2018/09/02 06:00 [entrez] AID - S0024-3205(18)30526-5 [pii] AID - 10.1016/j.lfs.2018.08.064 [doi] PST - ppublish SO - Life Sci. 2018 Oct 1;210:86-95. doi: 10.1016/j.lfs.2018.08.064. Epub 2018 Aug 29.