Modified Bushen Yiqi formula attenuates neutrophils recruitment to the lung in rats model of COPD via inhibiting the CXCL1/CXCL5/CXCL8-CXCR2 axis and its downstream STAT and SRC signaling pathways

Abstract

Abstract Background: Modified Bushen Yiqi formula (MBYF) demonstrates a therapeutic effect on patients with chronic obstructive pulmonary disease (COPD), however, its mechanism against COPD remains unclear. This study aims to explore the therapeutic effect and mechanisms of MBYF in a rat model of COPD.Methods: The therapeutic effect of MBYF(12.5 g/kg or 25 g/kg) on six-month cigarette smoke (CS)-induced COPD rats model was evaluated through pulmonary function test, inflammatory cell count in bronchoalveolar lavage fluid (BALF), and inflammatory cytokines in serum and BALF. The therapeutic mechanism was revealed by the RNA-sequencing using lung tissue in CS and CS+MBYF group and confirmed via immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot. Results: MBYF remarkably improved the pulmonary function in the rat model of COPD, ameliorated inflammatory cell accumulation in the lung, and reduced the level of inflammatory cytokines in pulmonary and systemic. Mechanistically, MBYF suppressed the chemotactic migration of neutrophils into the lung by down-regulating CXC motif chemokine ligands (CXCL)1/CXCL5/CXCL8-CXC chemokine motif receptor (CXCR)2 axis. Moreover, MBYF inhibited the activation of STAT1, STAT3, and SRC, which are the downstream signaling pathways of the chemokine-chemokines receptor.Conclusion: MBYF attenuated neutrophils recruitment to the lung in the rats model of COPD via inhibiting the CXCL1/CXCL5/CXCL8-CXCR2 axis and its downstream STAT and SRC signaling pathways. Our results support further investigation of MBYF as a promising therapy in the management of COPD.