Integrated Multiomics and Network pharmacology Reveal Glycyrrhiza Uralensis Extract Ameliorating Inflammatory Response in COPD Mice by Regulating Gut Microbiota, Metabolites and Genes

Glycyrrhiza Uralensis, known as "Liquorice" in Chinese, is a traditional medicinal plant acknowledged for its use as a dietary supplement for ailments including digestive disorders, menopausal symptoms, cough, and bacterial and viral infections. Despite its recognised advantages, there is little information concerning the effects and underlying mechanisms of Glycyrrhiza Uralensis in mitigating respiratory symptoms linked to chronic obstructive pulmonary disease (COPD).This study sought to evaluate the pharmacodynamics and mechanisms of action of the water extract of Glycyrrhiza Uralensis (GU) wild root in the treatment of COPD using comprehensive analyses that include gut microbiota evaluation, metabolomic analysis, network pharmacology and Molecular docking. The pharmacodynamics of GU were evaluated using weigth, lung function assessment, lung histopathological examination, and serum inflammatory factor level analysis in mice. Furthermore, we examined the diversity and composition of gut microbiota by microbial analysis. We undertook an extensive investigation of the principal components in the therapeutic benefits of GU on COPD utilizing metabolomics. Targets and pathways were find using network pharmacology. Additionally. Molecular docking and Western blotting approaches were employed to elucidate the binding mechanisms and expression levels of key targets. GU markedly enhanced the pulmonary function of COPD mice and mitigated the inflammatory responses. Metabolomics analysis predict the important pathways such as phenylalanine, tyrosine, and tryptophan production, phenylalanine metabolism, porphyrin metabolism, and fatty acid breakdown enhancing overall energy equilibrium and metabolic well-being. Network pharmacology demonstrated that GU suppressed the activation of the PI3K-Akt signalling pathways and resistance to EGFR tyrosine kinase inhibitors in the lung. Moreover, GU was discovered to reinstate the diversity and quantity of gut microbiota. Our findings, for the first time, indicate that GU have anti-COPD properties. This research enhances the therapeutic potential of Glycyrrhiza Uralensis Wild and requires additional investigation and advancement.