Objective To investigate the intervention effect of Jingfang Granules (荆防颗粒) on airway inflammation and airway remodeling in asthmatic mice based on lung-gut axis, and elucidate the underlying molecular mechanism. Methods BALB/c mice were randomly divided into control group, model group, Jingfang Granules low-, medium-, high-dose (1, 2, 4 g/kg) groups and dexamethasone (1 mg/kg) group. A mouse asthma model was established by ip ovalbumin/aluminum hydroxide. After drug intervention, levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) in serum and interleukin-1β (IL-1β), IL-6 in lung tissue were detected. Hematoxylin-eosin (HE), PAS and Masson staining were used to detect pathological changes in lung tissue of mice. Immunohistochemistry was used to detect mucin 5AC (MUC5AC) protein expression in lung tissue. Western blotting was used to detect the expressions of transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway, NOD nuclear factor-κB (NF-κB) signaling pathway in lung tissue and intestinal barrier related proteins. 16S rRNA sequencing, untargeted metabolomics and proteomics analyses were integrated to systematically explore the potential mechanism of Jingfang Granules in asthma intervention from a multi-omics perspective. Results Compared with model group, Jingfang Granules significantly reduced the levels of TNF-α in serum and IL-1β, IL-6 in lung tissue of asthma model mice (P < 0.01), increased the level of IFN-γ in serum (P < 0.01), significantly reduced the infiltration of inflammatory cells in lung tissue, decreased the expression of MUC5AC in lung tissue, inhibited the activity of TGF-β1/Smad2/3 signaling pathway, thereby alleviating airway mucus secretion and airway remodeling. The results of multi-omics analysis further indicated that Jingfang Granules could upregulate the expressions of Occludin, Claudin1 and ZO-1, promote intestinal barrier repair, regulate gut microbiota imbalance and fecal metabolic disorders, and inhibit the abnormal activation of the NOD-NF-κB signaling pathway. Conclusion Jingfang Granules may ameliorate airway inflammation and airway remodeling in asthmatic mice by repairing intestinal barrier function, improving gut microbiota structure, correcting fecal metabolic disorders, and modulating NOD-NF-κB signaling pathway.

Jingfang Granules  /  asthma  /  gut microbiota  /  lung-gut axis  /  metabolomics  /  NOD-NF-κB signaling pathway