Investigating the Underlying Mechanisms of Ma-Xing-Shi-Gan-Tang on Asthma via Metabolomics and Network Pharmacology.

OBJECTIVE

Ma-xing-shi-gan-tan (MXSGT) was first published in "Shang-han-lun". It functions as a heat-clearing agent, lung-clearing formula, and asthma reliever. This study aims to evaluate the therapeutic effect of MXSGT on asthma and elucidate its underlying mechanisms.

METHODS

Key components of MXSGT were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). A rat model of asthma induced by ovalbumin (OVA) was employed to assess MXSGT efficacy. The fundamental mechanisms of MXSGT in asthma treatment were investigated through metabolomic analysis, network pharmacology, and molecular docking.

RESULTS

MXSGT treatment demonstrated significant protective effects in OVA-induced asthmatic rats, evidenced by its suppression of inflammatory mediators including nuclear factor kappa B complex p65 (NF-κBp65), p38 mitogen-activated protein kinase (p38-MAPK), and transforming growth factor-β1 (TGF-β1). Metabolomic analysis revealed 9 MXSGT blood components and 12 differential metabolites associated with MXSGT treatment. Further analysis indicated that MXSGT's therapeutic benefit in asthma involves modulation of metabolic pathways such as the citric acid cycle (TCA cycle), alanine and aspartate metabolism, tyrosine metabolism, among others. Succinic acid was identified as the metabolite most prominently involved in these pathways. Additionally, network pharmacology identified TNF as a key target linking blood components and differential metabolites, mediating anti-asthma effects through MAPK and NF-κB signaling pathways.

CONCLUSION

Our findings demonstrate that MXSGT exerts anti-inflammatory effects in asthma treatment by inhibiting MAPK and NF-κB signaling pathways and regulating host metabolites and metabolic pathways. These insights provide novel perspectives on MXSGT's role in asthma management.