Exploring the Function of Fritillariae thunbergii Bulbus on the Inflammation Response in Cough Variant Asthma Mice Model Based on Metabolomics

Abstract

Cough variant asthma (CVA) is one of the primary causes of chronic cough. And we found that Fritillariae thunbergii Bulbus (FTB) exhibited promising antitussive and expectorant functions. Thus, we explore the role and mechanism of FTB on CVA based on metabolomics. CVA mice models were established using ovalbumin and treated with different concentrations of FTB (1–4 g/kg). Then cough numbers, airway resistance, inflammatory factor levels, inflammatory cell numbers, EOS contents, and lung histopathology were determined. Furthermore, TLR4-MyD88-NF-κB pathway-related protein expressions were evaluated. Besides, UPLC-MS/MS analysis was applied to detect serum differential metabolites of CVA mice with FTB treatment. We found that FTB showed obvious effects on CVA mice by reducing cough number and airway resistance, alleviating inflammation response in serum and BALF, and improving lung pathological damage. Furthermore, FTB decreased TLR4-MyD88-NF-κB pathway-associated protein expressions in the lung tissue of CVA mice. The results of metabolomics found that FTB recovered the levels of nucleosides, analogues, organic acids and derivatives as well as organoheterocyclic compounds in CVA mice serum, the modulation may relate to metabolic pathways, purine metabolism and regulation of lipolysis in adipocytes. FTB suppressed inflammation in CVA via inhibiting TLR4-MyD88-NF-κB signaling pathway and serum metabolic levels, indicating that FTB might act as a novel drug for treating CVA.