Lingganwuweijiangxin Decoction suppresses allergic airway inflammation in Guinea pigs with cough variant asthma by regulating the treg/Th17 balance and the JAK1/STAT6 signaling pathway

Lingganwuweijiangxin Decoction (LD) is an effective prescription widely used to treat cough variant asthma (CVA) in traditional Chinese medicine, although its mechanisms remain unclear. This study investigates the therapeutic effects and underlying mechanisms of LD on CVA. A guinea pig CVA model was treated with either LD or budesonide (BUD). Capsaicin aerosol-induced coughs were recorded. Pathological changes were then examined using hematoxylin and eosin staining, transmission electron microscopy, and Wright–Giemsa staining of bronchoalveolar lavage fluid (BALF). Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA expression levels of transcription factors forkhead box P3 (Foxp3), retinoic acid-related orphan receptor γt (RORγt), Janus kinase 1 (JAK1), signal transducer and activator of transcription 6 (STAT6), the transient receptor potential ankyrin 1 (TRPA1), and transient receptor potential vanilloid 1 (TRPV1) in lung tissue were detected by real-time reverse transcription polymerase chain reaction, and protein levels of these markers were assessed by Western blotting. Compared to the control group, the model group showed significantly more coughs, which were markedly reduced by LD treatment (<i>p</i> = 0.0083 and <i>p</i> = 0.0117). LD treatment also decreased inflammatory cell infiltration, alveolar epithelial hyperplasia, and mitochondrial swelling in ciliated cells, consistent with the lung tissue injury score (<i>p</i> &lt; 0.0001). LD significantly reduced the ovalbumin-induced elevation of TRPA1 (<i>p</i> &lt; 0.01 and <i>p</i> &lt; 0.0001), TRPV1 (<i>p</i> &lt; 0.01 and <i>p</i> &lt; 0.0001), and substance P (SP) levels (<i>p</i> &lt; 0.05). Moreover, LD treatment increased <i>Foxp3</i> mRNA (<i>p</i> = 0.0013) and protein expression (<i>p</i> &lt; 0.0001) and reduced <i>RORγt</i> mRNA (<i>p</i> &lt; 0.0001). LD also decreased <i>JAK1</i> and <i>STAT6</i> transcription (<i>p</i> = 0.0021, <i>p</i> &lt; 0.0001, respectively), with consistent effects observed at the protein level (<i>p</i> &lt; 0.0001). LD significantly reduced coughs and airway inflammation in the CVA guinea pig model by regulating TRPA1, TRPV1, SP, regulatory T cell/T helper 17 cell balance, and the JAK1/STAT6 signaling pathway. These effects were comparable to BUD, suggesting that LD may be a viable alternative treatment for CVA.