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Cited by 46Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisPulmonary Hypertension Research and TreatmentsAdenosine and Purinergic Signaling

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Asiaticoside might attenuate bleomycin‐induced pulmonary fibrosis by activating cAMP and Rap1 signalling pathway assisted by A2AR

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Luo, Jing, Zhang, Ting, Zhu, Chengwei, Sun, Junwei, Zhu, Wenjing, Ai, Wenxiu, Huang, Xiaoying, Wang, Xiaobing·2020·Journal of Cellular and Molecular Medicine
DOI 10.1111/jcmm.15505PMC PMC7348182
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Abstract

Asiaticoside (AS) has been reported to have protective effect on pulmonary fibrosis (PF). In this study, we aimed to explore the potential mechanism of the therapeutic role of AS and its relationship with A2AR in PF. Adenosine 2A receptor gene knockout (A2AR−/−) mice and wild‐type (WT) mice were used to establish bleomycin (BLM)‐induced PF models and were then treated with AS (50 mg/kg/d). Pulmonary inflammation and fibrosis were observed in the PF model with much higher severity in A2AR−/−mice than that in WT mice and AS significantly alleviated lung inflammation and fibrosis; however, it was less effective in A2AR−/− mice than in WT mice via histopathological analysis. Using RNA sequencing analysis, we found up‐regulated differentially expressed genes (DEGs) in BLM group were enriched in immune and inflammation‐associated pathways compared with control group. There were 242 common DEGs between down‐regulated in BLM vs control group and up‐regulated in BLM + AS vs BLM group, which were enriched in cAMP and Rap1 signalling pathways. Furthermore, the expression of five key factors of these two pathways including adenylate cyclase (ADCY1, ADCY5, ADCY8, cAMP and Rap1) were confirmed up‐regulated by AS with the presence of A2AR. Therefore, AS might attenuate BLM‐induced PF by activating cAMP and Rap1 signalling pathways which is assisted by A2AR, making it a promising therapeutic optional for PF.

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  • Asiaticoside attenuates bleomycin-induced pulmonary fibrosis by activating cAMP and Rap1 signalling pathways, thus inhibiting inflammation and fibrosis in lungs.

    “asiaticoside is known to attenuate bleomycin‐induced pulmonary fibrosis by activating cAMP and Rap1 signalling pathways, thus inhibiting inflammation and fibrosis in the lungs.”

    From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [115]

    The Results report reduced lung inflammation and collagen deposition after asiaticoside treatment in bleomycin-treated mice, alongside increased expression of components of the cAMP and Rap1 pathways. But the Discussion describes pathway-mediated attenuation as an assumption, and the Figure 7 caption calls the mechanism a hypothesis. The citing sentence presents that mechanism as established rather than tentative. (LLM, conf=0.88)

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Metadata

Authors
Luo, J., Zhang, T., Zhu, C., Sun, J., Zhu, W., Ai, W., Huang, X., & Wang, X.
Affiliations
  • First Affiliated Hospital of Wenzhou Medical University (CN)
  • The First People's Hospital of Wenling (CN)
Corresponding author
  • Huang, Xiaoying
  • Wang, Xiaobing
ORCID
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2020-06-16
Volume
24
Issue
14
Pages
8248-8261
ISSN
  • 1582-1838 (ISSN-L)
  • 1582-4934
DOI
10.1111/jcmm.15505
PMC
PMC7348182
OpenAlex
W3034522543
Cited by
46
References
3
Citations by year
2026: 5 · 2025: 11 · 2024: 9 · 2023: 11 · 2022: 9 · 2021: 1
FWCI
2.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81700062)
  • Natural Science Foundation of Zhejiang Province (LQ16H010003)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Keywords
asiaticoside, pulmonary fibrosis, bleomycin-induced lung injury, adenosine A2A receptor, adenylate cyclase, lung inflammation, differentially expressed genes, adenosine
MeSH terms
Cyclic AMP, Animals, Bleomycin, Disease Models, Animal, Immunohistochemistry, Male, Mice, Transgenic, Models, Biological, Pulmonary Fibrosis, Triterpenes, Signal Transduction, Computational Biology, Protective Agents, rap1 GTP-Binding Proteins, Gene Expression Profiling, Receptor, Adenosine A2A, Mice, Immunomodulation, Transcriptome

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