Huang Dan, Sun Chaoqun, Chen Min, Bai Shuyou, Zhao Xuanna, Wang Weiming, Geng Kang, Huang Wenbo, Zhao Tingting, Wu Bin, Zhang Guilin, Wu Dong, Xu Youhua
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, China.
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Front Pharmacol. 2022 Oct 13;13:994878. doi: 10.3389/fphar.2022.994878. eCollection 2022.
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 and experiments by establishing a mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that 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 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.
气道炎症和重塑是哮喘的关键病理变化,巨噬细胞激活在此过程中起重要作用。沉默调节蛋白1(SIRT1)通过影响哮喘中的巨噬细胞来减轻气道炎症。本研究旨在探讨SIRT1激动剂岩白菜素作为哮喘治疗药物的潜在益处及潜在机制。我们分别通过建立小鼠哮喘模型和使用肺泡巨噬细胞样细胞系MH-S进行了 和 实验。我们的结果表明, 哮喘小鼠比野生型小鼠表现出更严重的气道炎症和气道重塑。作为SIRT1的激活剂,岩白菜素减轻了野生型哮喘小鼠的哮喘气道病理,并减少了白细胞介素1β、IL-5、IL-6和基质金属蛋白酶9(MMP-9)的产生。然而,在 哮喘小鼠中或与SIRT1抑制剂EX-527联合给药后,岩白菜素的治疗效果显著减弱。进一步的实验表明,岩白菜素激活SIRT1可使核因子κB去乙酰化并阻碍其核转位,从而通过调节转录活性影响IL-1β、IL-5、IL-6和MMP-9的产生。我们的研究表明,岩白菜素可通过激活巨噬细胞中的SIRT1来改善哮喘诱导的气道炎症和重塑。