Study on the improvement of cough variant asthma by the Tongfu Zhike formula via the TLR4/MyD88/NF-κB signaling pathway.

Abstract

OBJECTIVE: Evaluation of the therapeutic effect of Tongfu Zhike Formula (TFZKF) on mice with cough variant asthma (CVA) and exploration of its mechanism of action in improving CVA. METHODS: The main chemical components of TFZKF were detected and analyzed using UHPLC-MS/MS. Network pharmacology was employed to investigate the potential targets of TFZKF in CVA. After grouping and drug administration, the number of coughs and cough latency were observed in CVA mice. White blood cell differential counts in BALF, serum levels of IgE, IL-4, IL-5, IL-13 and IFN-γ, as well as pathological changes in lung tissue were assessed. Western blot and RT-qPCR were used to analyze the protein expression levels and mRNA changes of TLR4, MyD88, and NF-κB in the lung tissue of CVA mice. RESULTS: A total of 495 chemical components were detected in TFZKF under both positive and negative ion modes. Network pharmacology analysis identified 199 potential targets related to TFZKF and CVA, and found close associations with the TLR4 and NF-κB signaling pathways. Animal experiments showed that, compared to the Model group, TFZKF significantly reduced the number of coughs, prolonged cough latency, decreased serum levels of IgE, IL-4, IL-5, and IL-13, reduced the total number of white blood cells, neutrophils, and eosinophils in BALF, alleviated inflammatory cell infiltration and fibrosis in lung tissue, and downregulated the protein and mRNA expression of TLR4, MyD88, and NF-κB. CONCLUSION: The interaction within the TLR4/MyD88/NF-κB signaling pathway may be a potential key target for the treatment of cough variant asthma.