title: Astragalus polysaccharide modulates ER stress response in an OVA-LPS induced murine model of severe asthma.
abstract: Endoplasmic reticulum (ER) stress has been recently revealed to play a pivotal role in the pathogenesis of severe asthma. Astragalus polysaccharide (APS), a major bioactive component from Astragalus membranaceus, exerts immunomodulatory and anti-inflammatory effects and has been shown to suppress ER stress in chronic diseases such as type-2 diabetes. However, the pharmaceutical application of APS in the treatment of severe asthma is unknown. The results obtained here indicate that APS significantly attenuates eosinophils and neutrophil-dominant airway inflammation by reducing the mRNA levels of Cxcl5, Il8, and chemokine (C-C motif) ligand 20 (Ccl20) and the protein levels of IL13RA and IL17RA. APS also inhibits the activation of unfolded protein response by decreasing the levels of ER stress markers such as C/EBP homologous protein (CHOP), which was associated with a reduction of PERK phosphorylation. Moreover, APS substantially blocks the nuclear translocation of ATF6 and NF-κB p65. Interestingly, we observed that APS markedly suppresses mucus hypersecretion by decreasing the levels of mucin (MUC) 5AC and MUC5B, which might be due to inhibition of goblet cells differentiation by suppressing the expression of IRE1β-correlated genes. In summary, APS can have potential pharmaceutical application in treatment of severe asthma.
authors.affiliation: Pediatric institution of Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing, 210023, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Pediatric institution of Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing, 210023, China.
authors.forename: Qiong-Qiong
authors.initials: QQ
authors.lastname: Xing
authors.affiliation: Pediatric institution of Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing, 210023, China.
authors.forename: Jian-Ya
authors.initials: JY
authors.lastname: Xu
authors.affiliation: Pediatric institution of Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing, 210023, China.
authors.forename: Dou
authors.initials: D
authors.lastname: Ding
authors.affiliation: Pediatric institution of Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing, 210023, China. Electronic address: zhaoxiahy@126.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D027883:Astragalus Plant / Q000737:chemistry; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing; D020397:Goblet Cells / Q000187:drug effects; D007073:Immunoglobulin E / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011134:Polysaccharides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018927:Anti-Asthmatic Agents; D007378:Interleukins; D008070:Lipopolysaccharides; D009077:Mucins; D010936:Plant Extracts; D011134:Polysaccharides; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Astragalus polysaccharide; Endoplasmic reticulum; Severe asthma