The effect of astragaloside IV on JAK2‐STAT6 signalling pathway in mouse model of ovalbumin‐induced asthma

Yang, Xinfu; Wang, Feida

doi:10.1111/jpn.13114

Cited by 17 publications

(10 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that AS-IV has pharmacological effects as an anti-oxidant, anti-inflammatory, immunomodulatory, antiviral, and antitumor agent. 27 In recent years, AS-IV has received attention in the prevention of respiratory diseases, such as asthma, 28 pulmonary fibrosis 29 and lung cancer. 30 However, there are few reports on the prevention of PM2.5-induced lung injury by AS-IV through modulation of the autophagic pathway.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Pei¹,

Wang²,

Huang³

et al. 2021

JIR

View full text Add to dashboard Cite

Introduction Prolonged exposure to air polluted with airborne fine particulate matter (PM2.5) can increase respiratory disease risk. Astragaloside IV (AS-IV) is one of the main bioactive substances in the traditional Chinese medicinal herb, Astragalus membranaceus Bunge. AS-IV has numerous pharmacological properties; whereas there are few reports on the prevention of PM2.5-induced lung injury by AS-IV through modulation of the autophagic pathway. This study aimed to investigate the protective effects and the underlying mechanisms of AS-IV in PM2.5-induced lung injury rats and rat alveolar macrophages (NR8383 cells). Methods The pneumotoxicity model was established by intratracheal injection of PM2.5 in rats, and PM2.5 challenge in NR8383 cells. The severity of lung injury was evaluated by wet weight to dry weight ratio and McGuigan pathology scoring. Inflammatory factors and oxidative stress were detected through ELISA. The expressions of p-PI3K, p-Akt, and p-mTOR proteins were analyzed by immunohistochemistry. Immunofluorescence and transmission electron microscopy were used to detect autophagosomes. The expressions of autophagy marker protein (LC3B and p62), PI3K/Akt/mTOR signaling and NF-κB translocation were detected by Western blot in lung tissue and NR8383 cells. Results After PM2.5 stimulation, rats showed severe inflammation and oxidative stress, along with inhibition of autophagy in lung tissue. AS-IV not only decreased pulmonary inflammation and oxidative stress by inhibiting nuclear factor kappa B translocation, but also regulated autophagy by inhibiting PI3K/Akt/mTOR signaling. After treatment with 3-methyladenine (a classic PI3K inhibitor, blocking the formation of autophagosomes), the protective effect of AS-IV on PM2.5-induced lung injury was further strengthened. In parallel, using Western blot, immunohistochemistry, and transmission electron microscopy, we demonstrated that AS-IV restore autophagic flux mainly through regulating the degradation of autophagosomes rather than suppressing the formation in vivo and in vitro. Conclusion Our data indicated that AS-IV protects from PM2.5-induced lung injury in vivo and in vitro by inhibiting the PI3K/Akt/mTOR pathway to regulate autophagy and inflammation.

show abstract

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Pei¹,

Wang²,

Huang³

et al. 2021

JIR

View full text Add to dashboard Cite

show abstract

“…Similarly, JAK2 controls white blood cells, a number of red blood cells and platelets that are correlated with severe asthma. Recent clinical validations indicate that inhibition of the JAK2/STAT6 signaling pathway may be considered for ovalbumin-induced asthma therapies [26]. Thus could confirm the strong association of JAK2, STAT3 and severe asthma.…”

Section: Discussionmentioning

confidence: 88%

Novel Comprehensive Bioinformatics Approaches to Determine the Molecular Genetic Susceptibility Profile of Moderate and Severe Asthma

Zayed

2020

IJMS

View full text Add to dashboard Cite

Background: Asthma is a chronic inflammatory condition linked to hyperresponsiveness in the airways. There is currently no cure available for asthma, and therapy choices are limited. Asthma is the result of the interplay between genes and the environment. The exact molecular genetic mechanism of asthma remains elusive. Aims: The aim of this study is to provide a comprehensive, detailed molecular etiology profile for the molecular factors that regulate the severity of asthma and pathogenicity using integrative bioinformatics tools. Methods: The GSE43696 omnibus gene expression dataset, which contains 50 moderate cases, 38 severe cases, and 20 healthy controls, was used to investigate differentially expressed genes (DEGs), susceptible chromosomal loci, gene networks, pathways, gene ontologies, and protein–protein interactions (PPIs) using an intensive bioinformatics pipeline. Results: The PPI network analysis yielded DEGs that contribute to interactions that differ from moderate-to-severe asthma. The combined interaction scores resulted in higher interactions for the genes STAT3, AGO2, COL1A1, CLCN6, and KSR for moderate asthma and JAK2, INSR, ERBB2, NR3C1, and PTK6 for severe asthma. Enrichment analysis (EA) demonstrated differential enrichment between moderate and severe asthma phenotypes; the ion transport regulation pathway was significantly enhanced in severe asthma phenotypes compared to that in moderate asthma phenotypes and involved PER2, GCR, IRS-2, KCNK7, KCNK6, NOX1, and SCN7A. The most enriched common pathway in both moderate and severe asthma is the development of the glucocorticoid receptor (GR) signaling pathway followed by glucocorticoid-mediated inhibition of proinflammatory and proconstrictory signaling in the airway of smooth muscle cell pathways. Gene sets were shared between severe and moderate asthma at 16 chromosome locations, including 17p13.1, 16p11.2, 17q21.31, 1p36, and 19q13.2, while 60 and 48 chromosomal locations were unique for both moderate and severe asthma, respectively. Phylogenetic analysis for DEGs showed that several genes have been intersected in phases of asthma in the same cluster of genes. This could indicate that several asthma-associated genes have a common ancestor and could be linked to the same biological function or gene family, implying the importance of these genes in the pathogenesis of asthma. Conclusion: New genetic risk factors for the development of moderate-to-severe asthma were identified in this study, and these could provide a better understanding of the molecular pathology of asthma and might provide a platform for the treatment of asthma.

show abstract

“…Many studies have demonstrated that AS-IV can protect the cardiovascular system, lungs, kidneys and brain, an effect attributed to its anti-inflammatory, antioxidant, anti-apoptotic and immunoregulation properties ( Yan et al, 2017 ; Meiqian et al, 2018 ; Zhang et al, 2019 ; Tan et al, 2020 ). It has been shown that AS-IV could counter inflammation through multiple signaling pathways, such as Toll like receptor four/nuclear factor–kappa B (TLR4/NF-κB) signaling pathway, mitogen-activated protein kinases (MAPK) signaling pathway, and Janus kinase two/signal transducer and activator of transcription 6 (JAK2/STAT6) signaling pathway ( Leng et al, 2019 ; Yang and Wang, 2019 ; Hsieh et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Relieves Atherosclerosis and Hepatic Steatosis via MAPK/NF-κB Signaling Pathway in LDLR−/− Mice

Zhang

Wang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Astragaloside IV (AS-IV) is the main active compound of Astragalus membranaceus. In this study, we investigated whether AS-IV could attenuate atherosclerosis and hepatic steatosis in LDLR−/−mice and its potential mechanisms. After 12 weeks of high fat diet, the LDLR−/−mice were randomly divided into four groups. Then, the mice were administrated with 0.9% saline or AS-IV (10 mg/kg) or atorvastatin (1.3 mg/kg) for 12 weeks. Serum lipid profiles and inflammatory cytokines were detected by ELISA, hepatic TC and TG by colorimetric enzymatic kits, gene expression by RT-qPCR, plaque sizes by H&E staining, Oil Red O, liver pathology by H&E staining, collagen content by Masson, α-SMA, caspase-3 and NF-κB p65 production by immunofluorescence staining. MAPK/NF-κB pathway and inflammation related proteins were detected by Western Blot. The results showed that AS-IV decreased the levels of serum lipids, reduced plaque area and increased plaque stability in HFD-induced LDLR−/− mice. AS-IV also decreased the levels of inflammatory cytokines in the serum, aortas and liver tissue, and NF-κB p65 in aortic roots. The phosphorylation of JNK, ERK1/2, p38 and NF-κB, and inflammatory proteins (iNOS, VCAM-1and IL-6) was inhibited in AS-IV-treated group. In summary, AS-IV inhibited inflammation to attenuate atherosclerosis and hepatic steatosis via MAPK/NF-κB signaling pathway in LDLR−/− mice.

show abstract

The effect of astragaloside IV on JAK2‐STAT6 signalling pathway in mouse model of ovalbumin‐induced asthma

Cited by 17 publications

References 33 publications

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Novel Comprehensive Bioinformatics Approaches to Determine the Molecular Genetic Susceptibility Profile of Moderate and Severe Asthma

Astragaloside IV Relieves Atherosclerosis and Hepatic Steatosis via MAPK/NF-κB Signaling Pathway in LDLR−/− Mice

Contact Info

Product

Resources

About