Aim of the study
This study was aimed at revealing the mechanism through which GPH protects against BA. Materials and
Conclusion
GPH was found to activate the PPAR signaling pathway, decrease the levels of Cyp4a12a and Cyp4a12b, and increase the levels of Adh7, Acaa1b and Gpat2, thereby regulating lipid metabolism disorder, decreasing the generation of inflammatory mediators and limiting lung injury.
Methods
The protective effect of GPH against BA was evaluated in a mouse model of BA induced by ovalbumin. Through integrated metabolomics and transcriptomics analysis, the most critical pathways were discovered. The effects of GPH in regulating these pathways was verified through molecular biology experiments and molecular docking.
Results
GPH have anti-BA effects. In plasma and lung tissue, 5 and 17 differentially expressed metabolites (DEMs), respectively, showed a reversed tendency in the GPH group compared with the model group; apart from gamma-aminobutyric acid and butyrylcarnitine, these DEMs might aid in BA diagnosis. The DEMs were involved primarily in the regulation of lipid metabolism, followed by glucose metabolism and amino acid metabolism. Transcriptomic analysis indicated that GPH modulated 268 differentially expressed genes (DEGs). Integration analysis of metabolomics and transcriptomics revealed that GPH might regulate the PPAR signaling pathway, thus affecting the expression of key gene targets such as Cyp4a12a, Cyp4a12b, Adh7, Acaa1b and Gpat2; controlling fatty acid degradation, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and other lipid metabolic pathways; and ameliorating BA. This possibility was confirmed through reverse-transcription quantitative polymerase chain reaction, western blotting, immunofluorescence and molecular docking.