Effective-components combination improves airway remodeling in COPD rats by suppressing M2 macrophage polarization via the inhibition of mTORC2 activity

Background: In chronic obstructive pulmonary disease (COPD), M2 macrophages release multiple tissue repair-related factors, leading to airway remodeling, a significant pathological characteristic. Meanwhile, effective-components combination (ECC), derived from Bufei Yishen formula (BYF), is an effective treatment for COPD. Purpose: To determine the potential mechanisms of ECC in airway remodeling in COPD by suppressing M2 macrophage polarization. Methods: We established a rat COPD Model using exposure to cigarette smoke and bacterial infection to investigate the efficacy of ECC. We also treated macrophages with IL-4 for 12 h to explore the in vivo effect of ECC on M2 macrophage polarization and mTORC2 signals. Results: The disease severity of COPD rats could be alleviated by ECC treatment, which improved pulmonary function and alleviated pathological injuries in lung tissue and the inflammatory cytokine levels. Meanwhile, ECC could ameliorate airway remodeling by reducing collagen deposition, hindering airway mucus hypersecretion and smooth muscle cell proliferation, and reducing the number of M2 macrophages in the lung tissues of COPD rats. Furthermore, with IL-4-induced macrophages, we found that ECC could suppress M2 macrophage polarization by decreasing the levels of M2 macrophage markers. Finally, we discovered that ECC inhibited mTORC2 activity by examining p-mTOR2481 and its downstream protein p-Akt(473). Conclusions: ECC exerts beneficial effects on airway remodeling in COPD rats, likely by suppressing M2 macrophage polarization via the inhibition of mTORC2 activity.