Asthma is one of the most common chronic disease characterized by recurrent respiratory symptoms such as wheezing, shortness of breath, chest tightness and coughing (Sockrider et al., 2020). Approximately 300 million people worldwide suffer from asthma (Stern et al., 2020). Although asthma mortality has declined globally over the past 25 years, asthma continues to place a heavy burden on society (Papi et al., 2018). Based on the level of granulocyte in the induced sputum, asthma can be categorized into four different phenotypes, namely eosinophilic asthma, neutrophilic asthma (NA), mixed granulocytic asthma and oligocytic asthma (da Cunha et al., 2016). Asthma with more than 61% neutrophil content in induced sputum is identified as NA (Simpson et al., 2006). Several studies have proposed that the presence of airway neutrophils may be a driver of airway inflammation and injury, especially in cases of severe asthma (Krishnamoorthy et al., 2018; Ray et al., 2017; Chen et al., 2021). Excessive airway neutrophilia is reported to be present in 20–30% of patients with asthma (Chung, 2016). These patients tend to have a poorer response to steroid, poor asthma control and a higher risk of exacerbation (Ray et al., 2017). There is growing evidence that neutrophil-induced airway inflammation is strongly associated with severe asthma and sudden death asthma (Chen et al., 2021). Given that conventional therapies are often ineffective for NA, there is an urgent need for effective alternative therapies.

Traditional Chinese Medicine (TCM) has a long history of treating asthma and has the advantage of synergistic effects of multiple components and targets. Xiaoqinglong decoction (XQLD) originates from Zhongjing Zhang's Treatise on Typhoid Fever and Miscellaneous Diseases, and is composed of Ephedrae herba (Ma-Huang, dried herbaceous stem of Ephedra intermedia Schrenk et C. A. Mey.), Cinnamomi ramulus (Gui-Zhi, dreid young branch of Cinnamomum verum J.Presl), Paeoniae radix alba (Bai-Shao, dried root of Paeonia lactiflora Pall), Asari radix et rhizoma (Xi-Xin, dried root and rhizome of Asarum heterotropoides F.Schmidt), Zingiberis Rhizoma (Gan-Jiang, died rhizome of Zingiberis offficinale Roscoe), Pinelliae rhizoma (fa-Ban-Xia, died tuber of Pinellia ternata (Thunb.) Makino), Schisandrae chinensis fructus (Wu-Wei-Zi, died ripe fruit of Schisandrae Chinensis (Turcz.) Baill), Glycyrrhizae Radix et rhizoma (Gan-Cao, processed dried root and rhizome of Glycyrrhiza glabra L.). (The name of all the plants in the article has been checked with http://mpns.kew.org). The dosage ratio of the herbs in XQLD is 3:5:5:1:3:3:3:3:3. It has been widely used in clinical practice, especially for its effectiveness and safety in the treatment of asthma (Wang et al., 2020; Li et al., 2023; Zhang et al., 2003). XQLD combines with fluticasone inhaler improves lung function and suppresses serum IL-6 levels in asthma patients in a clinical trial (Zhang et al., 2003). Li et al. find that modified XQLD has significant efficacy in children with cough-variant asthma, including reduction of cough symptoms, improvement of pulmonary function, attenuation of inflammatory response and enhancement of immunity (Li et al., 2023). Moreover, Kao ST et al. have confirmed the immunomodulatory effect of XQLD on allergen-induced airway inflammation in asthmatic mice (Kao et al., 2000). Wang B et al. find that XQLD increases autophagy levels, thereby reducing the accumulation of abnormal metabolites, alleviating airway inflammation and promoting asthma recovery in asthmatic rats (Wang et al., 2022). Pharmacologically, multiple components in XQLD have potent anti-inflammatory effects (Zheng et al., 2023; Xue et al., 2021a; Deng et al., 2021; Li et al., 2021a). The pathogenesis of NA is complex and XQLD contains multiple ingredients. Therefore, the mechanisms of XQLD in treating NA need to be further clarified.

Network pharmacology excels in illustrating the drug-disease-target relationships, and provides a basis for revealing the mechanisms of TCM (Zhang et al., 2019). In recent years, proteomics has become a powerful tool for finding innovative mechanisms and differentially expressed proteins (DEPs) (Monti et al., 2019). Tandem Mass Tags (TMT), an in vitro labeling technology developed by Thermo, has been widely used in the analysis of DEPs. TMT helps more and more researchers to clarify the underlying mechanism of diseases, especially in TCM research (Pan et al., 2021; Cheng et al., 2022). To the best of our knowledge, there are no studies reporting the efficacy and potential mechanisms and targeting signaling pathways of XQLD for NA. Hence, this study integrated network pharmacology, OVA/CFA-induced NA mouse model and proteomics analysis to investigate the efficacy and molecular mechanisms of XQLD for NA treatment.