AUTHOR=Ren An-qi , Wang Hui-jun , Zhu Hai-yan , Ye Guan , Li Kun , Chen Dao-feng , Zeng Tao , Li Hong 

TITLE=Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF-κB Pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.693298

DOI=10.3389/fphar.2021.693298

ISSN=1663-9812

ABSTRACT=<p><bold>Background and Aims:</bold><italic>Rabdosia japonica</italic> var. <italic>glaucocalyx</italic> is a traditional Chinese medicine (TCM) for various inflammatory diseases. This present work aimed to investigate the protective effects of <italic>R. japonica</italic> var. <italic>glaucocalyx</italic> glycoproteins on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism.</p><p><bold>Methods:</bold> Glycoproteins (XPS) were isolated from <italic>R. japonica</italic> var. <italic>glaucocalyx</italic>, and homogeneous glycoprotein (XPS5-1) was purified from XPS. ANA-1 cells were used to observe the effect of glycoproteins on the secretion of inflammatory mediators by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assay, immunofluorescence assay, and Western blot analysis were performed to detect macrophage polarization <italic>in vitro</italic>. The ALI model was induced by LPS via intratracheal instillation, and XPS (20, 40, and 80 mg/kg) was administered intragastrically 2 h later. The mechanisms of XPS against ALI were investigated by Western blot, ELISA, and immunohistochemistry.</p><p><bold>Results:</bold><italic>In vitro</italic>, XPS and XPS5-1 downregulated LPS-induced proinflammatory mediators production including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and nitric oxide (NO) and upregulated LPS-induced IL-10 secretion. The LPS-stimulated macrophage polarization was also modulated from M1 to M2. <italic>In vivo</italic>, XPS maintained pulmonary histology with significantly reducing protein concentration and numbers of mononuclear cells in bronchoalveolar lavage fluid (BALF). The level of IL-10 in BALF was upregulated by XPS treatment. The level of cytokines including TNF-α, IL-1β, and IL-6 was downregulated. XPS also decreased infiltration of macrophages and polymorphonuclear leukocytes (PMNs) in lung. XPS suppressed the expression of key proteins in the TLR4/NF-κB signal pathway.</p><p><bold>Conclusion:</bold> XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of <italic>R. japonica</italic> var. <italic>glaucocalyx</italic> in inflammation-linked diseases.</p>