Preventive and Therapeutic Effects of Thymol in a Lipopolysaccharide-Induced Acute Lung Injury Mice Model

Background/Aims: Formyl peptide receptors (FPRs) recognize different endogenous and exogenous molecular stimuli and mediate neutrophil activation. Dysregulation of excessive neutrophil activation and the resulting immune responses can induce acute lung injury (ALI) in the host. Accordingly, one promising approach to the treatment of neutrophil-dominated inflammatory diseases involves therapeutic FPR1 inhibition. Methods: We extracted a potent FPR1 antagonist from Garcinia multiflora Champ. (GMC). The inhibitory effects of GMC on superoxide anion release and elastase degranulation from activated human neutrophils were determined with spectrophotometric analysis. Reactive oxygen species (ROS) production and the FPR1 binding ability of neutrophils were assayed by flow cytometry. Signaling transduction mediated by GMC in response to chemoattractants was assessed with a calcium influx assay and western blotting. A lipopolysaccharide (LPS)-induced ALI mouse model was used to determine the therapeutic effects of GMC in vivo. Results: GMC significantly reduced superoxide anion release, the reactive oxidants derived therefrom, and elastase degranulation mediated through selective, competitive FPR1 blocking in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF)-stimulated human neutrophils. In cell-free systems, GMC was unable to scavenge superoxide anions or suppress elastase activity. GMC produced a right shift in fMLF-activated concentration-response curves and was confirmed to be a competitive FPR1 antagonist. GMC binds to FPR1 not only in neutrophils, but also FPR1 in neutrophil-like THP-1 and hFPR1-transfected HEK293 cells. Furthermore, the mobilization of calcium and phosphorylation of mitogen-activated protein kinases and Akt, which are involved in FPR1-mediated downstream signaling, was competitively blocked by GMC. In an in vivo study, GMC significantly reduced pulmonary edema, neutrophil infiltration, and alveolar damage in LPS-induced ALI mice. Conclusion: Our findings demonstrate that GMC is a natural competitive FPR1 inhibitor, which makes it a possible anti-inflammatory treatment option for patients critically inflicted with FPR1-mediated neutrophilic lung damage.

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Therapeutic Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Models of Pulmonary and Extrapulmonary Acute Lung Injury

Cell Transplantation ◽

10.3727/096368915x687499 ◽

2015 ◽

Vol 24 (12) ◽

pp. 2629-2642 ◽

Cited By ~ 22

Author(s):

Ling Liu ◽

Hongli He ◽

Airan Liu ◽

Jingyuan Xu ◽

Jibin Han ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Acute Lung Injury ◽

Lung Injury ◽

Therapeutic Effects

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Cordyceps Militaris Alleviates Severity of Murine Acute Lung Injury Through miRNAs-Mediated CXCR2 Inhibition

Cellular Physiology and Biochemistry ◽

10.1159/000430168 ◽

2015 ◽

Vol 36 (5) ◽

pp. 2003-2011 ◽

Cited By ~ 8

Author(s):

Sheng Liu ◽

Jian Tang ◽

Lei Huang ◽

Qirong Xu ◽

Xiang Ling ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Distress Syndrome ◽

Mrna Level ◽

Cordyceps Militaris ◽

Microvascular Endothelial Cells ◽

Mouse Lung ◽

Therapeutic Effects ◽

Beneficial Effects

Background/Aims: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are lethal diseases in humans, and the current treatments have limited therapeutic effects. Cordyceps militaris (CM) is a caterpillar-grown traditional medicinal mushroom, and has been used as a natural invigorant for longevity, endurance, and vitality in China. Recently, purified extracts from CM have been shown to have beneficial effects on various diseases including cancer. Nevertheless, a role of CM in ALI has not been examined previously. Methods: Here, we used a bleomycin-induced ALI model to study the effects of CM on the severity of ALI in mice. The levels of CXCR2, a receptor for Interleukin 8 (IL-8) in pulmonary microvascular endothelial cells, were examined in different experimental groups. The levels of microRNA (miR)-1321 and miR-3188 were also examined in lung samples and in CM. Adeno-associated viruses carrying miR-1321 and miR-3188 were injected into bleomycin-treated mice for evaluation their effects on the severity of ALI. Results: CM treatment significantly alleviated the severity of bleomycin-induced ALI in mice. The increases in lung CXCR2 by bleomycin were significantly reduced by CM at protein level, but not at mRNA level. CM contained high levels of 2 miRNAs (miR-1321 and miR-3188) that target 3'-UTR of CXCR2 mRNA to inhibit its expression. Overexpression of miR-1321 and miR-3188 in mouse lung through AAV-mediated gene therapy mimicked the effects of CM. Conclusion: CM may alleviate severity of murine ALI through miRNAs-mediated CXCR2 inhibition.

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The therapeutic effects of bone marrow-derived mesenchymal stromal cells in the acute lung injury induced by sulfur mustard

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1189-x ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 6

Author(s):

Yongwei Feng ◽

Qingqiang Xu ◽

Yuyan Yang ◽

Wenwen Shi ◽

Wenqi Meng ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lung Injury ◽

Lung Injury ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Sulfur Mustard ◽

Therapeutic Effects

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Therapeutic Effects of Baicalin on Lipopolysaccharide-Induced Acute Lung Injury in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x08005783 ◽

2008 ◽

Vol 36 (02) ◽

pp. 301-311 ◽

Cited By ~ 25

Author(s):

Kun-Lun Huang ◽

Chien-Sheng Chen ◽

Ching-Wang Hsu ◽

Min-Hui Li ◽

Hung Chang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Weight Ratio ◽

Histological Finding ◽

Neutrophil Infiltration ◽

Lavage Fluid ◽

Blue Dye ◽

Therapeutic Effects ◽

Lung Weight ◽

Lactate Dehydrogenase Activity

Baicalin is a flavonoid present in many traditional Chinese medicines. A number of studies show that baicalin has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The effect of baicalin in lipopolysaccharide (LPS)-induced acute lung injury is not well studied. In this study, typically acute lung injury was induced in rat by intratracheal injection of LPS, which increased lactate dehydrogenase activity and protein content in bronchoalveolar lavage fluid, wet/dry lung weight ratio, Evan's blue dye leakage, and neutrophil infiltration. Baicalin (20 mg/kg) was administrated 1 hour before or 30 min after LPS injection. Both pre and post-treatment with baicalin attenuated the increase of these parameters and improved histological finding. Our results suggest that baicalin has a therapeutic effect on LPS-induced acute lung injury.

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Fasudil Attenuates LPS-Induced Acute Lung Injury by Preventing Endothelial Dysfunction

10.20944/preprints201703.0225.v1 ◽

2017 ◽

Author(s):

Jingjing Wang ◽

Jian Xu ◽

Xinyun Zhao ◽

Weiping Xie ◽

Hong Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Rho Kinase ◽

Intercellular Junctions ◽

Intercellular Adhesion Molecule ◽

Mice Model ◽

Rock Inhibitor ◽

Histological Changes ◽

Endothelial Apoptosis ◽

Cytokine Levels

Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.

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