Salidroside Improves Cellular Senescence in COPD by Inhibiting the JAK2/STAT3 Pathway

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a respiratory illness, with cellular senescence recognized as an essential mechanism driving this chronic lung disease. Salidroside (Sal), a natural compound, is recognized for its anti-aging impacts. Therefore, this study aims to investigate the role and the underlying mechanism of Sal on airway epithelial cell senescence. Methods: In vitro experiments were performed by treating BEAS-2B cells with cigarette smoke extract (CSE), AG490 (Janus kinase 2 (JAK2) inhibitor), or Sal (40 μM, 80 μM, 160 μM). Moreover, senescence-associated β-galactosidase (SA-β-gal) staining and the manifestation of senescence-related genes were used to assess cellular senescence. The mRNA levels of cyclin-dependent kinase inhibitor 2a (p16) and cyclin-dependent kinase inhibitor 1a (p21) were evaluated. Furthermore, Western blot analysis was employed to determine the expression levels of p16, p21, Janus kinase 2 (JAK2), phosphorylated-JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-STAT3 (p-STAT3). Additionally, the cytokine levels associated with the senescence-associated secretory phenotype (SASP) were evaluated utilizing corresponding enzyme-linked immunosorbent assay kits. Results: In vitro, cellular experiments demonstrated that Human bronchial epithelial cells underwent senescence in response to CSE, as evidenced by elevated expression of p16 (p < 0.05) and p21 (p < 0.05), and promotion of senescence-associated secretory phenotype (SASP), as well as up-regulation of JAK2/STAT3 signaling pathway activity. AG490 treatment significantly ameliorated CSE-induced cellular senescence, resulting in down-regulation of the JKA2/STAT3 signaling pathway, alleviation of the senescence molecules p16 (p < 0.05), p21 (p < 0.05), p-JKA2 (p < 0.01) and p-STAT3 (p < 0.05). The inhibitor decreased the secretion of SASP cytokines, and decreased the activity of SA-β-gal. Additionally, Sal reduced p16 (p < 0.01) and p21 (p < 0.05) expression, potentially reversed CSE-induced cellular senescence, and inhibited the JAK2/STAT3 signaling pathway, as well as decreased SASP secretion and SA-β-gal activity. Conclusion: Sal reduces CSE-induced BEAS-2B cellular senescence by inhibiting the JAK2/STAT3 signaling pathway, providing a novel strategy for COPD treatment.