Bergenin ameliorates airway inflammation and remodeling in asthma by activating SIRT1 in macrophages to regulate the NF-κB pathway.

Abstract

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 1β, 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 κB and hinders its nuclear translocation, thereby affecting IL-1β, 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.

• Authors: Dan Huang, Chaoqun Sun, Min Chen, Shuyou Bai, Xuanna Zhao, Weiming Wang, Kang Geng, Wenbo Huang, Tingting Zhao, Bin Wu, Guilin Zhang, Dong Wu, Youhua Xu
• Journal: Frontiers in pharmacology (Front Pharmacol) Vol. 13 Pg. 994878 ( 2022) ISSN: 1663-9812 [Print] Switzerland
• PMID: 36313381 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Huang, Sun, Chen, Bai, Zhao, Wang, Geng, Huang, Zhao, Wu, Zhang, Wu and Xu.