Journal
FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.994878
Keywords
bergenin; SIRT1; NF-kappa B; asthma; macrophage
Categories
Funding
- National Science Foundation of Guangdong Province
- Guangdong Provincial Administration of Traditional Chinese Medicine [2021A1515011062]
- Project of Zhanjiang City [20221211]
- Affiliated Hospital of Guangdong Medical University [2020B01346, 2021A05077]
- [4SG21231G]
- [CLP202113001]
- [LCYJ 2017A003]
- [LCYJ 2020B008]
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This study found that the SIRT1 agonist bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 and regulating the transcriptional activity of nuclear factor kappa B.
Airway inflammation and remodeling are critical pathological changes in asthma, and macrophage activation plays a vital role in this process. Sirtuin 1 (SIRT1) reduces airway inflammation by affecting macrophages in asthma. This study aimed to investigate the potential benefit and underlying mechanism of the SIRT1 agonist bergenin as a treatment for asthma. We performed in vivo and in vitro experiments by establishing a Sirt1 ( fl/fl)-LysMcre mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that Sirt1 ( fl/fl)-LysMcre asthmatic mice exhibited more severe airway inflammation and airway remodeling than wild-type mice. As an activator of SIRT1, bergenin attenuated asthmatic airway pathology and reduced production of interleukins 1 beta, IL-5, IL-6, and matrix metalloproteinase 9 (MMP-9) in wild-type asthmatic mice. However, the therapeutic effects of bergenin were significantly attenuated in Sirt1 ( fl/fl)-LysMcre asthmatic mice or following coadministration with the SIRT1 inhibitor EX-527. Further experiments showed that activation of SIRT1 by bergenin deacetylates nuclear factor kappa B and hinders its nuclear translocation, thereby affecting IL-1 beta, IL-5, IL-6, and MMP-9 production by regulating transcriptional activity. Our study suggests that bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 in macrophages.
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