Investigating the Mechanism of Qifenggubiao Granules in COPD Treatment: An Integrated Exploration of Ferroptosis and the Gut–Lung Axis

Although an increasing number of studies focus on treating chronic obstructive pulmonary disease (COPD) through the gut–lung axis and immunomodulation, its underlying mechanisms remain poorly understood. Previous research has shown that Qifenggubiao granules (QFGB) exhibit obvious clinical efficacy in treating allergic rhinitis and chronic cough, demonstrating excellent antioxidant and anti-inflammatory properties. However, whether it can alleviate COPD by inhibiting ferroptosis remains unclear. Additionally, its immunomodulatory mechanisms in gut microbiota dysbiosis-related inflammation require further investigation. In this study, we found that QFGB not only suppresses oxidative stress but also inhibits ferroptosis by reducing lipid peroxide levels and increasing the expression of glutathione peroxidase 4 and xCT. The authors also discovered that QFGB significantly alleviates pulmonary dysfunction in COPD animal models by regulating macrophage polarization and remodeling the inflammatory immune microenvironment, thereby suppressing inflammation. Furthermore, 16 S ribosomal RNA sequencing and quantitative reverse transcription polymerase chain reaction analysis confirmed that QFGB modulates gut microbiota composition and bidirectionally regulates macrophage polarization in lung and intestinal tissues. These findings have been further validated in animal models of inflammatory bowel disease (IBD), demonstrating that QFGB can alleviate inflammation in IBD mice. This study demonstrates that QFGB can not only inhibit oxidative stress and ferroptosis in COPD but also regulate gut microbiota homeostasis and remodel the inflammatory microenvironment by modulating macrophage polarization via the gut–lung axis. The drug alleviates the severity of COPD and promotes functional recovery of the lung–gut organ axis. These findings have been further validated in animal models of IBD, demonstrating that QFGB can alleviate intestinal inflammation in mice.