Chronic obstructive pulmonary disease (COPD) poses a substantial global epidemiological challenge, ranking as the third leading cause of mortality worldwide (Agusti et al., 2023). It is primarily instigated by factors such as smoking and environmental exposures, with smoking standing as the predominant risk factor (Wheaton et al., 2019). The hallmark of COPD lies in heightened pulmonary inflammation, culminating in airway remodeling and subsequent pulmonary function decline (Christenson et al., 2022). Therefore, anti-inflammatory therapy represents the foundational strategy for COPD treatment (Agusti et al., 2023). Although glucocorticoids are the most prevalent anti-inflammatory therapies employed in COPD management, their effectiveness in slowing the decline of pulmonary function is limited. A significant proportion of patients exhibit poor responsiveness to glucocorticoids (Keenan et al., 2015). Moreover, long-term use of glucocorticoids raises concerns due to its association with adverse effects, including pneumonia, osteoporosis, muscle atrophy, and hyperglycemia (Zervas et al., 2013). Consequently, the pursuit of alternative anti-inflammatory treatments assumes paramount significance within the realm of clinical practice.

In China, traditional Chinese medicine (TCM) has been widely employed as a complementary therapy for COPD patients receiving standard treatment, with the goal of improving their quality of life and reducing adverse effects (Liao et al., 2020; Yao et al., 2021; Zhang et al., 2021, Zhang et al., 2021). The Modified Jiawei Bushen Yiqi formula (MBYF) is a specific TCM used clinically to address pulmonary inflammatory diseases such as asthma, COPD, idiopathic pulmonary fibrosis, and lung cancer (Kong et al., 2017; Kong et al., 2022; Wang et al., 2014, Wang et al., 2014). While the mechanisms of MBYF in treating asthma, idiopathic pulmonary fibrosis and lung cancer have been documented (Huang et al., 2021; Qin et al., 2022; Shi et al., 2023), its precise mechanism of action in COPD management remains unclear. MBYF comprises five herbs: Epimedium brevicornu Maxim (Herba Epimedii, HE) 20g, Astragalus membranaceus (Fisch.) Bunge (Astragali Radix, AR) 30g, Rehmannia glutinosa (Gaertn.) DC. (Rehmanniae Radix, RR) 15g, Scutellaria baicalensis Georgi (Radix Scutellariae, RS) 30g, and Paeonia lactiflora Pall. (Radix Paeoniae Rubra, RPR) 30g. The HPLC findings for MBYF have been previously reported (Huang and Dong, 2021; Shi et al., 2023). Studies have shown that compounds of MBYF, such as icariside II(Tang et al., 2022; Zhou et al., 2023), cycloastragenol (Zhu et al., 2022), and formononetin(Yi et al., 2020), significantly against airway inflammation and remodeling in asthma model. Thus, we propose that MBYF can alleviate pulmonary inflammation and airway remolding in COPD.

The IL17 signaling pathway plays a pivotal role in the pulmonary inflammatory response, involving the activation of Interleukin 17 (IL17) cytokines, specifically IL17A and IL17F (Li et al., 2019). IL17A and IL17F engage with their respective receptors on target cells, including bronchial and alveolar epithelial cells, fibroblasts, and macrophages (Ritzmann et al., 2022). Downstream signaling pathways are subsequently activated, culminating in the engagement of various transcription factors such as nuclear factor（NF)-κB and Mitogen-Activated Protein Kinases (MAPKs) (Amatya et al., 2017). This cascade of events leads to the production of pro-inflammatory cytokines (IL6, TNFα, IL1β, COX2), chemokines (CXCLs and CCLs), and matrix metalloproteinases (MMPs), thereby amplifying the inflammatory response (Amatya et al., 2017). These molecules contribute significantly to the recruitment and activation of immune cells, notably neutrophils, within the lung tissue (Ritzmann et al., 2022).

Neutrophils are key inflammatory cells in the pathogenesis of COPD(Stockley, 2002). IL17-induced chemokines, particularly CXCL1, CXCL5, and CXCL8 (also known as IL-8), act to recruit neutrophils to sites of inflammation (Barnes, 2018; Pignatti et al., 2005). The persistent activation of the IL17 pathway, coupled with the enduring presence of neutrophilic inflammation, ultimately leads to tissue damage, airway remodeling, and the characteristic decline in lung function observed in COPD(Christenson et al., 2022). Therefore, this study aims to assess the effect of MBYF on cigarette smoke (CS)-induced pulmonary inflammation in a rat model of COPD, with focus on neutrophil chemotaxis and the IL17 signaling pathway.